BACKGROUND: The transforming growth factor-beta1 (TGF-beta1) plays a key role in lung fibrosis. However, the mole?cular mechanisms involved in TGF-beta1-induced lung fibrosis are unclear. TGF-beta1 is the key inducer of myofibroblast transdifferentiation via de novo synthesis of alphasmooth muscle actin (alpha-SMA). Since TGF-beta1 signals through reactive oxygen species (ROS) and ROS have been shown to induce accumulation of extracellular matrix (ECM) in various tissues, this study examined if ROS play a role in TGF-beta1-induced fibronectin secretion and alpha-SMA expression in human lung fibroblasts, MRC-5 cells. METHODS: Growth arrested and synchronized MRC-5 cells were stimulated with TGF-beta1 (0.2-10 ng/ml) in the presence or absence of N-acetylcysteine (NAC) or diphenyleneiodonium (DPI) for up to 96 hours. Dichlorofluorescein (DCF)- sensitive cellular ROS were measured by FACScan and secreted fibronectin and cellular alpha-SMA by Western blot analysis. RESULTS: TGF-beta1 increased the level of fibronectin secretion and alpha-SMA expression in MRC-5 cells in a dose- dependent manner. Both NAC (20 and 30 mM) and DPI (1 and 5 microM significantly inhibited TGF-beta1-induced fibronectin and alpha-SMA upregulation. The TGF-beta1-induced cellular ROS level was also significantly reduced by NAC and DPI. CONCLUSIONS: The results suggest that NADPH oxidase-dependent ROS play an important role in TGF-beta1-induced fibronectin secretion and alpha-SMA expression in MRC-5 cells, which leads to myofibroblast transdifferentiation and progressive lung fibrosis.
Acetylcysteine ; Actins* ; Blotting, Western ; Extracellular Matrix ; Fibroblasts* ; Fibronectins* ; Fibrosis ; Humans* ; Lung* ; Muscle, Smooth* ; Myofibroblasts ; NADP ; Pulmonary Fibrosis ; Reactive Oxygen Species* ; Transforming Growth Factor beta1 ; Transforming Growth Factors* ; Up-Regulation

PURPOSE: Due to its size and locatin, the liver is frequently injured in abdominal trauma. Recently, nonoperative management for liver injuries has been extended due to the development CT imaging, intensive care units, and their equipment and techniques. Herein, patients with traumatic liver injury were analyzed to evaluate its treatment and prognostic factors. METHODS: From 2001, January to 2003, July, 65 patients at our facility were confirmed to have traumatic liver injury. The operative or nonoperative managements were decided on the basis of the systolic blood pressure if no peritoneal irritation sign was noted. If the systolic blood pressure was stable, or recovered to within the normal range following hydration and transfusion at the emergency room, patients were managed nonoperatively. Hemodynamically unstable patients were managed operatively. The data were analysed using the SPSS program (Chi-squared tests and logistic regression analyses). RESULTS: 48 patients were treated nonoperatively, with 3 mortalities. The overall mortality rate was 15.8%, but only 6.4% in the nonoperative management group, compared to 67% in operative management group. In a Multivariate analysis the systolic blood pressure was found to be a reliable factor in traumatic liver injury and the mentality and ISS (injury severity score) reliable in finding complications in the nonoperative management group. The mentality was found statistically reliable for determining mortality in the operative management group, with the exception for the systolic blood pressure. CONCLUSION: The systolic blood pressure was an important indicator when considering the treatment plan in traumatic liver injury. An extensive study will be required that incorporates both nonoperative and operative management groups.
Blood Pressure ; Emergency Service, Hospital ; Humans ; Intensive Care Units ; Liver* ; Logistic Models ; Mortality ; Multivariate Analysis ; Reference Values

BACKGROUND: This study was undertaken to analyze the necessity of deflating cuff volume to maintain intracuff pressure of the laryngeal mask airway (LMA) under 44 mmHg in general anesthesia with propofol and N2O. METHODS: In 168 surgical patients, LMA was inserted (male: #5, female: #4) and the cuff was sealed with air under positive pressure ventilation with 7-8 ml/kg of tidal volume. After measuring the initial intracuff pressure (P0), the intracuff volume (V0) of LMA and peak inspiratory pressure (PIP0), N2O (50%) was administered, and the time for the intracuff pressure to reach a pressure of 44 mmHg (T44), the intracuff volume for the intracuff pressure to reduce to P0 (Vdef), the N2O inhaled time and the number of patients who needed deflation were recorded. RESULTS: P0, V0, PIP0 were 24+/-7.5 mmHg, 17+/-2.8 ml, 13+/-3.8 cmH2O in males and 27+/-8.2 mmHg, 14+/-2.3 ml, 13+/-4.0 cm H2O in females, respectively. The number of patients who needed cuff deflation after inhaling N2O was 17 (18.5%) in males and 36 (47.4%) in females. T44 and Vdef were 27+/-16 min, 1.9+/-0.8 ml in males and 26+/-21 min and 1.3+/-0.6 ml in females, respectively. The necessity for LMA cuff deflation was related to P0, V0, and the N2O inhaled time in males and to P0 and the N2O inhaled time in females (P <0.05). CONCLUSIONS: In anesthesia with N2O, if the initial intracuff pressure of LMA is high and the duration of anesthesia prolonged, careful monitoring of the intracuff pressure is necessary.
Anesthesia ; Anesthesia, General ; Female ; Humans ; Inhalation ; Laryngeal Masks* ; Male ; Nitrous Oxide ; Positive-Pressure Respiration ; Propofol ; Tidal Volume

BACKGROUND: Endotoxin stimulates nitric oxide synthase (NOS) and the free radical nitric oxide (NO) is produced by NOS, which vasodilates the smooth muscle of pulmonary vessels. Otherwise, endotoxemia stimulates the release of cyclooxygenase (COX) products, which may modify hypoxic pulmonary vasoconstriction (HPV). We also observed the effect of nonselective NOS inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on receptor-mediated acetylcholine (Ach)/bradykinin (BK) induced vasoconstriction and receptor independent HPV in E.coli lipopolysaccharide (LPS) induced septic isolated rat lungs. METHODS: Four hours before surgical instrumentation for lung isolation, we administered saline (1 ml) to the control group (n = 15), E.coli LPS (20 mg/kg) to the LPS group (n = 14) and LPS (30 mg/kg) the nitric oxide synthase inhibitor, L-NAME (15 mg/kg) to the LPS + L-NAME group (n = 14), intraperitoneally. In 43 isolated rat lungs perfused with physiologic salt-albumin- blood mixture, angiotensin II 0.2 microgram was injected into the perfusion circuit, to confirm pulmonary vascular reactivity in each isolated lung. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. We observed the pulmonary arterial pressure at each challenge, ten minutes after the last HPV, 0.01, 0.1, 1.0 microgram of Ach and 1, 3, 10 microgram of BK were injected. PAP and static lung compliance were measured. RESULTS: The baseline pulmonary artery pressure in the LPS group higher than in the controls and HPV in the LPS group was changed compared to the controls but in the LPS + L-NAME it was higher than in the controls. The administration of Ach 0.1, 1.0 microgram and BK 3, 10 microgram causedpulmonary vasoconstriction and the vasoconstrictions of BK were dosage-dependent. Lung stiffness in the LPS and LPS + L-NAME groups were higher than those of the controls. CONCLUSIONS: Vascular constriction of pulmonary vessels and increased lung stiffness by Ach and BK might be the result of the endothelial injury. But pulmonary vasoconstriction and stiffness by Ach and BK were similar in the LPS and LPS + L-NAME groups, showing that factors other rather than excessive NO production might be involved in endothelial injury.
Acetylcholine ; Angiotensin II ; Animals ; Arterial Pressure ; Constriction ; Endotoxemia ; Lung Compliance ; Lung* ; Muscle, Smooth ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Perfusion ; Prostaglandin-Endoperoxide Synthases ; Pulmonary Artery ; Rats* ; Surgical Instruments ; Vasoconstriction* ; Ventilation

BACKGROUND: The failure to achieve satisfactory anesthesia following the administration of local anesthetic agents in acute inflammatory tissues is a recognized clinical phenomenon. Many inflammatory mediators can reduce the threshold of nociception during inflammation, and histamine, one of the most important inflammatory mediator, may attenuated local anesthetic effect during inflammation. The purpose of this study was to investigate if histamine can antagonize a lidocaine induced nerve block in vitro. METHODS: Recordings of the compound action potentials (CAP) of A-fiber components were obtained from the isolated sciatic nerves of male Sprague-Dawley rats. The nerve sheath of the sciatic nerve was removed and desheathed nerve was mounted in a recording chamber. Single pulse stimuli (0.5 msec, supramaximal stimuli) were repeatedly applied (2 Hz) to one end of the nerve and CAP recordings were made at the other. The effect of histamine on the suppression of CAP by lidocaine and the effect of histamine on the recovery time to the nerve block by lidocaine were measured. RESULTS: Compared with the baseline amplitude, the amplitudes of CAP were 11.7+/-4.1% for the lidocaine group, 18.3+/-4.6% for the lidocaine histamine 0.05% group, and 26.1+/-5.6% for the lidocaine histamine 0.5% group. Nerve block recovery times were: 38.6+/-3.5 min for the modified Krebs group, 29.8+/-4.2 min for histamine 0.05% in the modified Krebs group, and 19.2+/-1.1 min for histamine 0.5% in the modified Krebs group. CONCLUSIONS: Histamine shortened the recovery time induced by lidocaine. We suggest that histamine may significantly attenuate the effects of local anesthetics in inflammed tissue.
Action Potentials ; Anesthesia ; Anesthetics ; Anesthetics, Local ; Histamine* ; Humans ; Inflammation ; Lidocaine* ; Male ; Nerve Block* ; Nociception ; Rats, Sprague-Dawley ; Sciatic Nerve

BACKGROUND: Although the incidence of postoperative residual curarization (PORC) following the use of intermediate-acting neuromuscular blocking agents is lower than that of longer-acting neuromuscular blocking agents, it has been reported in many studies. We compared the incidence of PORC following either rocuronium or vecuronium given by intermittent bolus or continuous infusion dosing. METHODS: Ninety-eight patients were included in this study. Neuromuscular blocking drugs were administered based solely on clinical criteria, and the reversal agent pyridostigmine was given to all patients. Residual block following rocuronium infusion (Group R-I), rocuronium bolus (Group R-B), vecuronium infusion (Group V-I), or vecuronium bolus dosing (Group V-B) was evaluated on arrival in the postanesthesia care unit. Neuromuscular function was assessed acceleromyographically (using TOF-Watch(R) to measure the train-of-four (TOF) ratio) and also clinically. PORC was defined as a TOF ratio of < 0.8. RESULTS: The incidence of PORC on arrival in the postanesthesia care unit was 20% in Group R-I, 23% in Group R-B, 42% in Group V-I, and 19% in Group V-B. Mean TOF ratio in Group V-I was less than those of the other groups (P < 0.05). CONCLUSIONS: PORC is still common following vecuronium or rocuronium, even after the block is antagonized, if neuromuscular blocking agents are administered according to clinical criteria alone.
Anesthesia Recovery Period ; Humans ; Incidence ; Neuromuscular Blockade ; Neuromuscular Blocking Agents ; Pyridostigmine Bromide ; Vecuronium Bromide*

BACKGROUND: Sevoflurane is characterized by the lack of an unpleasant odor, airway irritation and its low blood/gas partition coefficient (0.68), which provides rapid and smooth induction. Inhaled induction with sevoflurane is commonly used in pediatric patients, but not in adult patients. This study was designed to investigate the time to completion of LMA insertion and end-tidal sevoflurane concentration during induction with sevoflurane 8% and N2O 50%, after midazolam administration, in adults. METHODS: Twenty eight patients, aged 20(-60) years, were administered intravenous midazolam 30 microgram/kg and after one minute, sevoflurane 8% and N2O 50% were inhaled with tidal-volume breathing. One minute after loss of consciousness, jaw thrust and mouth opening were checked and an LMA was inserted. The end-tidal concentration of sevoflurane, and the times to loss of consciousness and completion of insertion were recorded. The mean arterial pressure and heart rate were also recorded. RESULTS: From initiation of sevoflurane and N2O inhalation, it took 48 +/- 14 seconds until loss of consciousness, and 143 +/- 19 seconds until the completion of LMA insertion. The end-tidal sevoflurane concentration was 4.1 +/- 0.6% at loss of consciousness, 5.0 +/- 0.7% at one min after loss of consciousness, and 4.1 +/- 0.5% after LMA insertion. In all patients LMA insertion was successful and satisfactory. After LMA insertion, compared to baseline, the mean arterial pressure was reduced and the heart rate increased. CONCLUSIONS: After small-dose of midazolam, inhaled induction with sevoflurane 8% and N2O 50% allowed successful and satisfactory LMA insertion in adults.
Adult ; Arterial Pressure ; Heart Rate ; Humans ; Inhalation ; Jaw ; Laryngeal Masks ; Midazolam* ; Mouth ; Nitrous Oxide ; Odors ; Respiration ; Unconsciousness

BACKGROUND: It is recommended not to exceed an intracuff pressure of 22 mmHg. We evaluated many factors affecting the intracuff pressure of an endotracheal tube during general anesthesia using nitrous oxide. METHODS: Eighty adult patients undergoing surgery under general anesthesia using inhalation of nitrous oxide via a large-volume low-pressure cuffed standard tube (Vygon(R)) were enrolled. They were randomly divided into 4 groups according to sex and tube size; group M-1 (n = 20): male, 7.0 mm internal diameter (ID); group M-2 (n = 21): male, 7.5 mm; group F-1 (n = 21): female, 6.5 mm; group F-2 (n = 18): female, 7.0 mm. Specific cuff compliance of the tubes were 8.7 - 9.0nl/torr/ml and residual volumes of tubes of ID 6.5, 7.0 and 7.5 mm were 7.7 +/- 0.4, 11.1 +/- 0.5 and 10.9 +/- 0.5 ml, respectively. Sealing volume (SV), sealing pressure (SP), peak inspiratory pressure (PIP) and tracheal transverse diameter (TD) were measured. When the intracuff pressure reached 22 mmHg cuff volume (DV1) was deflated to SP and the elapsed time to the first deflation point (1-CP22) were recorded. Factors affecting the need for cuff deflation were analyzed. RESULTS: There were no correlations between SP or SV and TD. The incidence of need for cuff deflation was 30% and 38.1% in group M-1 and M-2, and 52.4% and 27.8% in group F-1 and F-2, respectively. The need for cuff deflation was significantly correlated with SP and duration of anesthesia in males and with SP in females (P < 0.05). CONCLUSIONS: Factors affecting the need for cuff deflation to maintain intracuff pressure below 22 mmHg were SP and duration of anesthesia in males, and SP in females and not SV/RV, TD or the size of the tube.
Adult ; Anesthesia ; Anesthesia, General* ; Compliance ; Female ; Humans ; Incidence ; Inhalation ; Male ; Nitrous Oxide* ; Residual Volume

BACKGROUND: The effect of a continuous infusion of ketamine on the cortisol and hyperglycemic response induced by surgery was studied in patients undergoing an abdominal hysterectomy under enflurane anesthesia. METHODS: Twenty adult female patients were randomly allocated to two groups receiving intravenous ketamine (0.3 mg/kg initially, followed by a continuous infusion at a rate of 0.15 mg/kg/h) (ketamine group, n = 10) or normal saline (control group, n = 10) 2 min after intubation. Hemodynamic responses, serum cortisol and glucose concentrations were measured before induction, 2 min after intubation, 2 min after incision, at closure of peritoneum and 5 min after extubation. Inspired and expired concentrations of enflurane were also evaluated. RESULTS: There were no significant differences in hemodynamic responses, inspired and expired concentrations of enflurane, serum cortisol and glucose concentrations between the two groups. As compared with the values before induction, significant increases were seen in serum cortisol (control: 2.3-2.6 times, ketamine: 2-2.2 times) and glucose concentrations (control: 1.2-1.3 times, ketamine: 1.3 times) at closure of peritoneum and 5 min after extubation in both groups (P<0.05). CONCLUSIONS: Continuous infusion of an analgesic dose of ketamine could not abolish the increases in serum cortisol and glucose induced by abdominal surgery under enflurane anesthesia.
Adult ; Anesthesia ; Anesthesia, General* ; Enflurane ; Female ; Glucose ; Hemodynamics ; Humans ; Hydrocortisone* ; Hysterectomy ; Intubation ; Ketamine* ; Peritoneum

BACKGROUND: It is generally accepted that propofol does not inhibit hypoxic pulmonary vasoconstriction (HPV). However, because the previous studies for the effects of propofol on HPV were established in vivo, the effects of physiologic variables could not be ruled out. Therefore, we investigated the effects of various concentrations of propofol on HPV at isolated rat lungs and the relationship of these effects of propofol on HPV and endothelium-derived relaxing factor (EDRF) and an ATP-dependent K+ channel which were candidates as the mechanism of HPV. METHODS: In 30 isolated rat lungs, after three hypoxic challenges for 5 minutes, we administered saline in the control group, N(G)-nitro-L-arginine methyl ester (L-NAME) in the L group and glibenclamide in the G group followed by three hypoxic challenges for 5 minutes. In addition, we studied the effects of various concentrations of propofol on HPV in the three groups. RESULTS: L-NAME and glibenclamide did not alter baseline pulmonary arterial pressure but L-NAME significantly enhanced HPV. Clinical concentrations of propofol did not affect HPV and high concentrations of propofol inhibited HPV. The pretreatment of L-NAME and glibenclamide did not alter the inhibition of HPV even at high concentrations of propofol. CONCLUSIONS: The EDRF and ATP-dependent K+ channel did not largely contribute to baseline pulmonary arterial tone but EDRF might be released and downregulate HPV. Clinical concentrations of propofol did not inhibit HPV but high concentrations of propofol inhibited HPV. In addition, the mechanism of inhibition of HPV at high concentrations of propofol did not relate to the EDRF pathway and ATP-dependent K+ channel.
Animals ; Arterial Pressure ; Endothelium-Dependent Relaxing Factors ; Glyburide* ; Lung* ; NG-Nitroarginine Methyl Ester* ; Propofol* ; Rats* ; Vasoconstriction*