Jin Kyoung Kim

Greater hemodynamic instability with histidine-tryptophan-ketoglutarate solution than University of Wisconsin solution during the reperfusion period in living donor liver transplantation.

OBJECTIVE University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the 2 most commonly used liver preservation solutions. The aim of this study was to compare cardiovascular stability, acid-base status, and potassium concentrations between patients who received grafts preserved in either UW or HTK solution in orthotopic liver transplantation (OLT). PATIENTS AND METHODS In this retrospective study, 87 patients who underwent living donor OLT were divided into 2 groups: UW (n = 28) and HTK (n = 59). Group HTK was subdivided into group NF-HTK (n = 31; nonflushed before reperfusion) and group F-HTK (n = 28; flushed before reperfusion). We determined mean arterial pressure (MAP) and heart rate every minute for 5 minutes after reperfusion and the maximum change in these values and incidence of postreperfusion syndrome (PRS). Body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were compared at 5 minutes before and 5 and 30 minutes after reperfusion. RESULTS The maximum decreases in MAP within 5 minutes after reperfusion were significantly greater in both the NF-HTK and the F-HTK groups. The rate of PRS was significantly greater in the NF-HTK compared with the UW group. Flushing with HTK solution decreased the rate of PRS; there was no significant difference between the F-HTK and UW groups. All serial changes in body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were similar among the 3 groups. CONCLUSIONS The incidence of PRS was greater using HTK compared with UW solution during the reperfusion period. Therefore, careful hemodynamic management is advised when using HTK solution.

Regulation of slowly activating potassium current (IKs) by secretin in rat pancreatic acinar cells

1 The secretagogue‐activated K+ conductance is indispensable for the electrogenic Cl− secretion in exocrine tissue. In this study, we investigated the effect of secretin and other cAMP‐mediated secretagogues on the slowly activating voltage‐dependent K+ current (IKs) of rat pancreatic acinar cells (RPAs) with the whole‐cell patch clamp technique. 2 Upon depolarization, RPAs showed IKs superimposed upon the instantaneous background outward current. Secretin (5 nm), vasoactive intestinal peptide (5 nm), forskolin (5 μm), isoprenaline (10 μm) or 3‐isobutyl‐1‐methylxanthine (IBMX, 0.1 mm) increased the amplitude of IKs two‐ to fourfold. 3 The physiological concentration of secretin (50 pm) had a relatively weak effect on IKs (160 % increase), which was significantly enhanced by transient co‐stimulation with carbachol (CCh) (10 μm). However, the secretin‐induced production of cAMP, which was measured by enzyme‐linked immunosorbent assay, was not augmented by co‐stimulation with CCh. 4 This study is the first to demonstrate the regulation of K+ channels in RPAs by cAMP‐mediated agonists. The IKs channel is a common target for both Ca2+ and cAMP agonists. The vagal stimulation under the physiological concentration of secretin facilitates IKs, which provides an additional driving force for Cl− secretion.

Combined carbamazepine and pregabalin therapy in a rat model of neuropathic pain

BACKGROUND Carbamazepine and pregabalin have proven effects against neuropathic pain. Carbamazepine blocks voltage-dependent Na(+) channels, whereas pregabalin blocks voltage-dependent Ca(2+) channels. The authors hypothesized that the co-administration of these drugs would synergistically reduce neuropathic pain. METHODS Neuropathic pain was induced by L5 nerve ligation in Sprague-Dawley rats. To determine their ED(50) values, carbamazepine and pregabalin were orally administered at 0.3, 3, 10, or 30 mg kg(-1). The drugs were then co-administered at 0, 1/4×ED(50), 1/2×ED(50), 1.5×ED(50), and 2×ED(50) to determine the ED(50) and ED(75) values of the drugs in combination. Allodynia was determined using the von Frey hair test and dose-effect curves and isobolograms were used to investigate drug interactions. Levels of the acute reactive protein c-Fos in the dorsal horn were evaluated as an indicator of pathological nerve excitation. RESULTS At ED(50) levels, carbamazepine and pregabalin did not exhibit synergism, but doses higher than ED(75) were found to be synergistic. The combination index was 0.18 (strong synergy) and dose reductions were 35.7-fold for carbamazepine and 6.8-fold for pregabalin when co-administered when compared with a single administration at ED(75). The percentage allodynia relief was only 60% for carbamazepine and 80% for pregabalin by single administration, whereas their co-administration relieved allodynia by 100%. Furthermore, treatment decreased c-Fos expression in the dorsal horn, but expressional differences between animals treated with carbamazepine plus pregabalin were not significantly different from those treated with single drug. CONCLUSIONS Carbamazepine and pregabalin ameliorate neuropathic pain synergistically at higher doses.

A Prospective, Randomized Comparison of the Effects of Inhaled Sevoflurane Anesthesia and Propofol/ Remifentanil Intravenous Anesthesia on Salivary Excretion During Laryngeal Microsurgery

BACKGROUND:One of the goals of anesthesia for laryngeal microsurgery is to provide a clear surgical view, and therefore anesthetics that produce less saliva are desirable. Sevoflurane inhalation anesthesia and total IV anesthesia with propofol/remifentanil are widely used for anesthesia during laryngeal microsurgery; however, few rigorous comparisons of the effects of sevoflurane and propofol/remifentanil on salivation have been performed. METHODS:Forty subjects undergoing laryngeal microsurgery were randomly assigned for sevoflurane or propofol/remifentanil anesthesia. We prospectively compared the salivary flow rates, compositions, the number of suction episodes required to clearly view the laryngeal lesions before the main procedures, and residual secretion volume after the procedure in both groups. RESULTS:The mean salivary excretion rate was significantly higher in the propofol/remifentanil group than in the sevoflurane group (0.53 ± 0.39 vs 0.28 ± 0.15 mL/min, P < 0.001). Before starting the main procedure, the number of suction episodes required to clearly view the laryngeal lesions was also higher in the propofol/remifentanil group (5.0 ± 2.3 vs 2.1 ± 1.5, P < 0.001). Mean residual secretion in the oral cavity and oropharynx after the procedure was greater in the propofol/remifentanil group (2.13 ± 0.59 vs 0.45 ± 0.32 mL, P < 0.001). In addition, a significant difference in chloride levels in collected secretion was noted (sevoflurane; 93 ± 19 vs propofol/remifentanil; 135 ± 58 U/L, P = 0.004). CONCLUSIONS:Salivary excretion under propofol/remifentanil anesthesia is greater than under sevoflurane anesthesia during laryngeal surgery.

Hypoxia-augmented constriction of deep femoral artery mediated by inhibition of eNOS in smooth muscle

In contrast to the conventional belief that systemic arteries dilate under hypoxia, we found that α-adrenergic contraction of rat deep femoral artery (DFA) is largely augmented by hypoxia (HVC(DFA)) while hypoxia (3% Po(2)) alone had no effect. HVC(DFA) was consistently observed in both endothelium-intact and -denuded vessels with partial pretone by phenylephrine (PhE) or by other conditions (e.g., K(+) channel blocker). Patch-clamp study showed no change in the membrane conductance of DFA myocytes by hypoxia. The RhoA-kinase inhibitor Y27632 attenuated HVC(DFA). The nitric oxide synthase inhibitor [nitro-L-arginine methyl ester (L-NAME)] and soluble guanylate cyclase inhibitor [oxadiazole quinoxalin (ODQ)] strongly augmented the PhE-pretone, while neither of the agents had effect without pretone. NADPH oxidase type 4 (NOX4) inhibitors (diphenylene iodonium and plumbagin) also potentiated PhE-pretone, which was reversed by NO donor. No additive HVC(DFA) was observed under the pretreatment with L-NAME, ODQ, or plumbagin. Western blot and immunohistochemistry analysis showed that both NOX4 and endothelial nitric oxide synthase (eNOS) are expressed in smooth muscle layer of DFA. Various mitochondria inhibitors (rotenone, myxothiazol, and cyanide) prevented HVC(DFA). From the pharmacological data, as a mechanism for HVC(DFA), we suggest hypoxic inhibition of eNOS in myocytes. The putative role of NOX4 and mitochondria requires further investigation. The HVC(DFA) may prevent imbalance between cardiac output and skeletal blood flow under emergent hypoxia combined with increased sympathetic tone.

Effect of preoperative skull block on pediatric moyamoya disease

OBJECT Stable hemodynamics, normocapnia, and adequate pain relief are considered important factors in the reduction of neurological complications in pediatric patients undergoing encephaloduroarteriomyosynangiosis (EDAMS) operations for the treatment of moyamoya disease. A preoperative skull block may reduce hemodynamic fluctuations and hypo- or hyperventilation due to emergence delirium or oversedation and provide adequate pain relief, thereby reducing postoperative morbidity. METHODS Pediatric patients (age 3-13 years) undergoing EDAMS surgery for moyamoya disease were randomly divided into a nerve block (NB) group (18 cases) or control group (21 cases). The treatment group patients received a preoperative NB (0.25% 5-8 ml bupivacaine mixed with 20-40 mg methylprednisolone) targeting the supraorbital, supratrochlear, auriculotemporal, and posterior auricular nerves. Patients in the control group did not receive NB. General anesthesia with sevoflurane was induced in both groups. RESULTS In the NB group, stable hemodynamic parameters were obtained with a lower sevoflurane concentration than in the control group. For delirious awakening, the odds ratio in the control group was 4.9 compared with the NB group. Pain and analgesic requirement were higher in the control patients than in the NB-treated patients during the postanesthesia care unit stay. However, the arterial CO(2) tension in the postanesthesia care unit did not differ between the 2 groups. The odds ratio in the control group for the rate of morbidity (cerebral infarction and reversible ischemic neurological deficits) during the first 24 hours following the operation was 3.2 compared with the NB group. CONCLUSIONS The use of skull block during EDAMS surgery provided easy hemodynamic control, calm awakening, and better pain relief and may be related to the reduced postoperative morbidity.

Differential effects of acute hypoxia on the activation of TRPV1 by capsaicin and acidic pH

Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable cation channel activated by a variety of physicochemical stimuli. The effect of hypoxia (

Requirement of Pretone by Thromboxane A2 for Hypoxic Pulmonary Vasoconstriction in Precision-cut Lung Slices of Rat

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