Mechanisms of direct inhibitory action of propofol on uterine smooth muscle contraction in pregnant rats.

BACKGROUND: Although propofol directly inhibits uterine smooth muscle contraction, the mechanisms of this effect are still unknown. The current study aimed to clarify the mechanisms of the inhibitory effect of propofol on oxytocin-induced uterine smooth muscle contraction by measuring (1) the concentration of intracellular free Ca(2+) ([Ca(2+)](i)) simultaneously with muscle tension, (2) the amount of intracellular inositol 1,4,5-triphosphate ([IP(3)](i)), and (3) voltage-dependent Ca(2+) channel (VDCC) activity. METHODS: Uterine smooth muscle tissues were obtained from pregnant rats (in late gestation). [Ca(2+)](i) with isometric tension was monitored by the 500-nm light emission ratio of preloaded Ca(2+) indicator fura-2. [IP(3)](i) and VDCC activity were measured by radioimmunoassay and patch clamp techniques, respectively. The uterine smooth muscle was stimulated by 20 nm oxytocin and exposed to propofol (10(-7) approximately 10(-4) m). RESULTS: Propofol had significant inhibitory effects on oxytocin-induced uterine smooth muscle contraction and increased [Ca(2+)](i) in pregnant rats in a dose-dependent manner, without affecting the agonist-receptor binding affinity. Propofol inhibited the increase in [IP(3)](i) induced by oxytocin. Propofol also inhibited VDCC activity in both activated and inactivated states. The solvent Intralipid had no effects on these parameters. CONCLUSIONS: Propofol inhibits oxytocin-induced uterine smooth muscle contraction, at least in part, by decreasing [Ca(2+)](i) without affecting agonist-receptor binding; the inhibitory effect of propofol on [Ca(2+)](i) might be mediated both by a decrease in [IP(3)](i) and by inhibition of VDCC activity.

Production of compound A under low-flow anesthesia is affected by type of anesthetic machine.

PURPOSE: The purpose was to compare the concentrations of compound A in inspired gas breathed by patients produced by different types of anesthetic machines under prolonged sevoflurane low-flow anesthesia. METHODS: The anesthetic machines tested were Excel 210 SE (Datex-Ohmeda, Louisville, CO), Cicero (Dräger, Lübeck, Germany), and AS/3 ADU (Datex-Ohmeda, Louisville, CO). Anesthesia expected to last more than four hours was maintained with 2.0% sevoflurane and nitrous oxide (0.5 L x min(-1))/oxygen (0.5 L x min(-1)). The concentrations of compound A, obtained from the inspiratory limb of the circle system, were measured using a gas chromatograph. RESULTS: When Excel and Cicero were used, concentrations of compound A increased steadily from the baseline values to 28 and 29 (mean) ppm, respectively, at two hours after exposure to sevoflurane and became constant. There was no significant difference between the concentrations of compound A produced by these anesthetic machines. In contrast, the new anesthetic machine AS/3 was associated with lower concentrations of compound A (6 ppm at one hour, P <0.05 compared with Excel and Cicero), and the concentration did not change significantly thereafter. CONCLUSION: In spite of the use of a conventional carbon dioxide (CO2) absorbent with strong bases, the anesthetic machine AS/3 with a small volume of canister/soda lime (900 ml/700 ml) produced lower concentrations of compound A than those produced by the other machines.

[Changes in sedative level during induction of anesthesia using a single volatile anesthetic].

We investigated the changes in sedative level during induction of anesthesia using a single volatile anesthetic, sevoflurane, compared with the changes when propofol and sevoflurane were used. We used a bispectral index (BIS) monitor (Aspect, Newton, USA) to monitor the sedative level. Thirty patients were randomly divided into one group receiving sevoflurane alone (S group, n = 15) and another group receiving propofol and sevoflurane (PS group, n = 15). The S group received 5% sevoflurane with nitrous oxide 6 l.min-1 and oxygen 3 l.min-1 via a face mask, while the PS group received propofol 1.5 mg.kg-1 i.v. followed by step-wise increasing sevoflurane up to 5%. Induction times, as assessed by loss of eyelash reflex, were 32 s in the PS group and 65 s in the S group. The decrease in the BIS value was smooth in the S group, whereas it increased transiently and varied greatly in the PS group. Two patients in the PS group showed body movement during induction of anesthesia, and the BIS values in both cases transiently exceeded 60. BIS monitor is useful for monitoring the sedative level during induction of anesthesia, and induction using a single volatile anesthetic such as sevoflurane is smooth.

Different inhibitory effects of volatile anesthetics on T- and L-type voltage-dependent Ca2+ channels in porcine tracheal and bronchial smooth muscles.

BACKGROUND: The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs). METHODS: Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution. RESULTS: The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (approximately 30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle. CONCLUSIONS: The existence of the T-type VDC in bronchial smooth muscle and the high sensitivity of this channel to volatile anesthetics seem to be, at least in part, responsible for the different reactivities to the anesthetics in tracheal and bronchial smooth muscles.

Celite-activated viscometer Sonoclot can measure the suppressive effect of tranexamic acid on hyperfibrinolysis in cardiac surgery.

PURPOSE: To investigate the usefulness of the celite-activated viscometer Sonoclot for monitoring fibrinolytic status in cardiac surgery, we demonstrated the effectiveness of high doses of tranexamic acid, an antifibrinolytic agent, in reducing postoperative bleeding. METHODS: Thirty-two American Society of Anesthesiologists (ASA) physical status III patients who required cardiac surgery with cardiopulmonary bypass (CPB) were studied. Anesthesia was induced by a high dose of fentanyl and midazolam with oxygen and was maintained by the intermittent administration of these agents. Patients were divided into two groups: the control group (n = 15) and patients receiving tranexamic acid (TA; n = 17). The TA group received a high dose (50 mg/kg) of TA twice, once before and once after CPB. The percentage diminishing rate of the Sonoclot tracing 15 min after maximum clot signal (DR(15)) and the amount of postoperative bleeding were measured. RESULTS: After CPB, DR(15) in the control group (mean 28.3%) increased significantly by 45%, and the DR(15) in the TA group (16.1%) was significantly lower than that in the control group. The amount of postoperative bleeding in the TA group (546 ml) was significantly less, by 34%, than that in the control group (829 ml). CONCLUSION: Prophylactic administration of high-dose TA in cardiac surgery reduces postoperative bleeding, and this effect is consistent with changes in the diminishing rate using Sonoclot. The celite-activated viscometer Sonoclot is recommended for use in cardiac surgery for rapid assessment of fibrinolytic status.

Interaction between volatile anesthetics and hypoxia in porcine tracheal smooth muscle.

UNLABELLED: We investigated the direct interaction between the volatile anesthetics, isoflurane and sevoflurane, and hypoxia in porcine tracheal smooth muscle in vitro by simultaneously measuring muscle tension and intracellular concentration of free Ca(2+) ([Ca2+]i). Muscle tension was measured by using an isometric transducer, and [Ca2+]i was measured by using fura-2, an indicator of Ca2+. Under the condition of bubbling with 95% O2/5% CO2, [Ca2+]i was increased by 1 microM carbachol with a concomitant contraction. Volatile anesthetics significantly inhibited both carbachol-induced muscle contraction and increase in [Ca2+]i. Hypoxia bubbled with 95% N(2)/5% CO2 inhibited the muscle contraction by 30% with an increase in [Ca2+]i by 20%. Exposure to hypoxia substantially enhanced the inhibitory effects of these anesthetics on carbachol-induced muscle contraction, whereas the decreases in [Ca2+]i were significantly prevented by hypoxia. Under Ca2+-free conditions, hypoxia significantly decreased the muscle contraction by 20%; however, it still increased [Ca2+]i by 15%. Exposure to the anesthetics significantly enhanced the inhibitory effect of hypoxia on the muscle contraction; however, it appeared to have little effect on [Ca2+]i. Hypoxia inhibits airway smooth muscle contraction independently of intracellular Ca2+, and it substantially potentiates the inhibitory effects of volatile anesthetics on airway smooth muscle contraction. IMPLICATIONS: Hypoxia inhibits agonist-induced tracheal smooth muscle contraction with an increase in free Ca2+ [Ca2+]i, which comes from intracellular Ca2+ stores. Hypoxia also potentiates the inhibitory effect of volatile anesthetics on airway smooth muscle contraction. Conversely, there is a possibility that the treatment of asthmatic patients with oxygen partially attenuates the inhibitory effect of volatile anesthetics on airway smooth muscle contractility.

Carbon dioxide absorbents containing potassium hydroxide produce much larger concentrations of compound A from sevoflurane in clinical practice.

UNLABELLED: We investigated the concentrations of degraded sevoflurane Compound A during low-flow anesthesia with four carbon dioxide (CO(2)) absorbents. The concentrations of Compound A, obtained from the inspiratory limb of the circle system, were measured by using a gas chromatograph. In the groups administered 2 L/min fresh gas flow with 1% sevoflurane, when the conventional CO(2) absorbents, Wakolime(TM) (Wako, Tokyo, Japan) and Drägersorb(TM) (Dräger, Lübeck, Germany), were used, the concentrations of Compound A increased steadily from a baseline to 14.3 ppm (mean) and 13.2 ppm, respectively, at 2 h after exposure to sevoflurane. In contrast, when the other novel types of absorbents containing decreased or no potassium hydroxide/sodium hydroxide, Medisorb(TM) (Datex-Ohmeda, Louisville, CO) and Amsorb(TM) (Armstrong, Coleraine, Northern Ireland), were used, Compound A remained at baseline (<2 ppm) throughout the study. In the groups administered 1 L/min fresh gas flow with 2% sevoflurane, Wakolime(TM) and Drägersorb(TM) produced much larger concentrations of Compound A (35.4 ppm and 34.2 ppm, respectively) at 2 h after exposure to sevoflurane. Medisorb(TM) showed measurable concentrations of Compound A (8.6 ppm at 2 h), but they were significantly smaller than those produced by the two conventional absorbents. In contrast, when Amsorb(TM) was used, Compound A concentrations remained at baseline throughout the study period. IMPLICATIONS: Carbon dioxide absorbents containing potassium hydroxide/sodium hydroxide produce much larger concentrations of Compound A from sevoflurane in clinical practice. An absorbent containing neither potassium hydroxide nor sodium hydroxide produces the smallest concentrations of Compound A.

[Clinical features and outcomes of mechanically ventilated patients with acute respiratory failure during treatment with immunosuppressive drugs].

We examined clinical features and outcomes of mechanically ventilated patient (n = 11) retrospectively who had developed acute respiratory failure during treatments with immunosuppressive drugs. The mean APACHE II score was 22.6, and the mean lung injury score was 2.9. In eight patients chest X-ray and computed tomography showed interstitial pneumonia. Fungus and/or cytomegalovirus were isolated most often from patients with interstitial pneumonia. Observed mortality (72.7%) was significantly (P < 0.001) higher than predicted mortality (45.1%) in the APACHE II score. Patients, who were complicated with septic shock caused by fungus infection, showed poor mortality. These results suggest that the fungus and cytomegalovirus infections might be associated with poor prognosis in patients with acute respiratory failure during treatment with immunosuppressive drugs.

Low-temperature modification of the inhibitory effects of volatile anesthetics on airway smooth muscle contraction in dogs.

BACKGROUND: Because exposure to low temperature can modify the effect of volatile anesthetics on airway smooth muscle contraction, this study was conducted to investigate low-temperature modifications of the inhibitory effects of isoflurane and sevoflurane on canine tracheal smooth muscle tone by simultaneously measuring the muscle tension and intracellular concentration of Ca2+ ([Ca2+]i) and by measuring voltage-dependent Ca2+ channel activity. METHODS: [Ca2+]i was monitored by the 500-nm light emission ratio of preloaded fura-2, a Ca2+ indicator. Isometric tension was measured simultaneously. Whole cell patch clamp recording techniques were used to observe voltage-dependent Ca2+ channel activity in dispersed muscle cells. Isoflurane (0-3.0%) or sevoflurane (0-3%) was introduced to a bath solution at various temperatures (37, 34, or 31 degrees C). RESULTS: Low temperature (34 or 31 degrees C) reduced high-K+-induced (72.7 mm) muscle contraction and increased [Ca2+]i, but it enhanced carbachol-induced (1 microm) muscle contraction with a decrease in [Ca2+]i. The volatile anesthetics tested showed significant inhibition of both high-K+-induced and carbachol-induced airway smooth muscle contraction, with a concomitant decrease in [Ca2+]i. The inhibition of the carbachol-induced muscle contraction by volatile anesthetics was abolished partially by exposure to low temperature. Volatile anesthetics and low-temperature exposure significantly inhibited voltage-dependent Ca2+ channel activity of the smooth muscle. CONCLUSIONS: Exposure of airway smooth muscle to low temperature leads to an increase in agonist-induced muscle contractility, with a decrease in [Ca2+]i. The inhibition of voltage-dependent Ca2+ channel activity by exposure to low temperature and by volatile anesthetics cam be attributed, at least in part, to the decrease in [Ca2+]i.

[Clinical evaluation of accuracy of a new disposable pump (Syrinjector) for continuous epidural infusion].

We evaluated the accuracy of a new disposable pump (Coopdech Syrinjector), which employed the negative pressure made by injecting fluid into the pump for continuous epidural infusion. Thoracic epidural catheter was placed at the T6-T8 level prior to the lung surgery. The continuous epidural infusion of 0.25% bupivacaine at 2 or 3 ml.h-1 was started immediately after the surgery. The residual volume of bupivacaine was recorded. From our results, the injection speed of Syrinjector was satisfactory for clinical use of continuous epidural infusion of bupivacaine. However, when this pump is reused or the volume of the residual local anesthetics is less than 10 ml, the infusion accuracy will be potentially imprecise.

Predictive variables of hypothermia in the early phase of general anesthesia.

UNLABELLED: Core temperature decreases precipitously for 1 h and then decreases slowly for 2-3 h after the induction of general anesthesia. We investigated the predictive variables of hypothermia by measuring peripheral skin temperature and total body fat (TBF). We studied 60 adult patients who required general anesthesia with isoflurane. The following variables were measured preoperatively: right palmar skin temperature by using an infrared thermometer and skin thickness at arm and scapula by using a standard caliper. TBF was calculated by using the regression equation of Durnin and Womersley. Rectal temperature, taken to represent core temperature, was measured during the operation. The gradient of hypothermia induced by general anesthesia was divided into two parts: 1) a precipitous decrease for the first hour and 2) a slow decrease for the following 2-3 h. Preoperative palmar skin temperature had a significant linear relationship with the precipitous decrease in temperature over the first hour (r = 0.69, P < 0.0001), and TBF had a significant linear relationship with the subsequent slow decrease in temperature (r = 0. 63, P < 0.0001). By simple measurements, we can predict the extent of hypothermia in the early phase of general anesthesia and prevent its onset by using body-warming techniques. IMPLICATIONS: After the induction of general anesthesia, palmar skin temperature had a linear relationship with the precipitous decrease in rectal temperature over the first hour, and total body fat had a linear relationship with the subsequent decrease in temperature. Thus, by simple measurements, we can predict the extent of hypothermia in the early phase of general anesthesia.

[Utility of an infrared ear thermometer as an intraoperative core temperature monitor].

We investigated the utility of an infrared ear thermometer (M 10, Terumo) as an intraoperative core temperature monitor. Temperatures of the axilla and inner ear were measured before and after anesthesia. Bladder, rectal, and forehead deep temperatures were continuously measured using a core temperature monitor (CTM-205, Terumo) during anesthesia. At the same time, the temperature of the inner ear was measured 4 times every 15 minutes (twice from cephalad and twice from caudal directions). There were no significant differences in the measured inner ear temperatures, either between directions of measurement or between the 1st and 2nd measurements. The inner ear temperature showed a close correlation with rectal, bladder, forehead deep, and axillary temperatures (r = 0.72-0.79, P < 0.01). The smallest temperature difference in this study was found to be that between the inner ear and forehead deep temperatures (-0.10), and the limit of agreement between these temperatures was also the smallest (0.81). In conclusion, we recommended the use of an infrared ear thermometer as an intraoperative core temperature monitor, especially in lower abdominal surgery, in which neither rectal nor bladder temperature monitoring is reliable.

The direct effects of heparin and protamine on canine tracheal smooth muscle tone.

UNLABELLED: Heparin and protamine are used for cardiopulmonary bypass in cardiac surgery; however, the direct effects and mechanisms of these drugs on airway smooth muscle tone are still not fully known. We investigated the in vitro effects of these drugs on canine tracheal smooth muscle by measuring the muscle tension and intracellular Ca2+ concentration ([Ca2+]i) and by measuring inward Ca2+ currents (I(Ca)) through voltage-dependent Ca2+ channels. [Ca2+]i was monitored by the 500-nm light emission ratio of preloaded Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of the drugs on I(Ca) in freshly dispersed smooth muscle cells. Heparin (0.12-120 U/mL), protamine (0.15-150 U/mL), or heparin-protamine complex (4:5 U/U) was introduced into a bath solution. Protamine and heparin-protamine complex dose-dependently inhibited both carbachol-induced contraction of the muscle and increase in [Ca2+]i. These drugs also decreased the I(Ca) of the muscle cells and shifted the inactivation curve to a more negative potential. Heparin itself had a slight enhancing effect on carbachol-induced muscle contraction without changing [Ca2+]i. Protamine and heparin-protamine complex can decrease the agonist-induced increase in [Ca2+]i by the inhibition of voltage-dependent Ca2+ channels both in the activated and inactivated states. IMPLICATIONS: Protamine and heparin-protamine complex inhibited carbachol-induced canine tracheal smooth muscle contraction by inhibiting the increase in intracellular concentration of free Ca2+. These drugs can decrease the agonist-induced increase in intracellular Ca2+ by the inhibition of voltage-dependent Ca2+ channels in both the activated and inactivated states.

Inhibitory effects of diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells.

BACKGROUND: Benzodiazepines have a direct bronchodilator action in airway smooth muscle, but the mechanisms by which these agents produce muscle relaxation are not fully understood. The current study was performed to identify the effects of the benzodiazepines diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells. METHODS: Whole-cell patch-clamp recording techniques were used to evaluate the effects of the benzodiazepines diazepam (10(-8) to 10(-3) M) and midazolam (10(-8) to 10(-3) M) on inward Ca2+ and outward K+ channel currents in dispersed canine tracheal smooth muscle cells. The effects of the antagonists flumazenil (10(-5) M) and PK11195 (10(-5) M) on these channels were also studied. RESULTS: Each benzodiazepine tested significantly inhibited Ca2+ currents in a dose-dependent manner, with 10(-6) M diazepam and 10(-5) M midazolam each causing approximately 50% depression of peak voltage-dependent Ca2+ currents. Both benzodiazepines promoted the inactivated state of the channel at more-negative potentials. The Ca2+-activated and voltage-dependent K+ currents were inhibited by diazepam and midazolam (> 10(-5) M and > 10(-4) M, respectively). Flumazenil and PK11195 had no effect on these channel currents or on the inhibitory effects of the benzodiazepines. CONCLUSIONS: Diazepam and midazolam had inhibitory effects on voltage-dependent Ca2+ channels, which lead to muscle relaxation. However, high concentrations of these agents were necessary to inhibit the K+ channels. The lack of antagonized effects of their antagonists is related to the non-gamma-aminobutyric acid-mediated electrophysiologic effects of benzodiazepines on airway smooth muscle contractility.

The usefulness of celite-activated thromboelastography for evaluation of fibrinolysis.

PURPOSE: Although thromboelastography is useful for measuring both coagulability and fibrinolysis, it takes about two hours to measure all parameters including fibrinolytic rate. The present study aimed to investigate the usefulness of celite-activated thromboelastography (TEGc) to evaluate fibrinolytic status in non-cardiac surgery. METHODS: Whole blood samples were obtained from 30 patients for non-cardiac surgery, and used for measurements of both native TEG (TEGn) and TEGc. The final concentration of 1% (w/v) celite was used for TEGc. RESULTS: Time for measurement of the fibrinolytic rate (FR) of TEGc in patients (56.7 +/- 4.0 min) was less than half that of FR of TEGn (123.3 +/- 15.6 min) (P < 0.05), suggesting a more rapid assessment of fibrinolytic status. A linear relationship was observed between FR values of TEGc and those of TEGn (r = 0.93, P < 0.0001), suggesting the usefulness of the fibrinolytic parameter of TEGc. CONCLUSION: TEGc is a useful technique for a more rapid assessment of fibrinolytic status.

[The effect of scalp infiltration with bupivacaine on blood coagulability and fibrinolysis in neurovascular surgery].

We investigated the effect of scalp infiltration with bupivacaine on blood coagulability and fibrinolysis in neurovascular surgery. Patients were randomly divided into two groups: scalp infiltration group (who received scalp infiltration with 0.5% bupivacaine prior to surgical incision, n = 7) and control group (n = 6). The blood coagulability and fibrinolysis were measured before and after surgical incision using a thromboelastogram (Thromboelastograph C-3000, Haemoscope). In the control group, the reaction and coagulation times were significantly shortened (30% and 23%, respectively, P < 0.05) and the maximum amplitude, which reflects coagulability, increased significantly (21%, P < 0.01) compared to each presurgical value. The scalp infiltration prior to the surgical incision prevented these reactions (P < 0.05). The fibrinolytic rate did not change in either group. We conclude that scalp infiltration prior to surgical incision is beneficial for attenuating an increase in blood coagulability, which could induce perioperative complications due to associated systemic diseases (i.e. hypertension, diabetes, ischemic heart disease, etc.).

[The effect of alpha-glucosidase inhibitor on burning epigastralgia in dumping syndrome: a case report].

Dumping syndrome results from a rapid passage of carbohydrate in the small intestine after gastric surgery. A 50-year-old man developed the syndrome after surgery for peptic ulcer. He often complained of burning epigastralgia after meals. Various methods of treatment had only a limited effect. Acarbose, alpha-glucosidase inhibitor, suppresses the breakdown of carbohydrates in the small intestine and consequently reduced osmolarity. The patient had a dramatic improvement in the dumping syndrome including epigastralgia, diarrhea and perspiration with an administration of acarbose 50 mg. There was no intractable side effect. Preprandial administration of acarbose is a reasonable treatment in the case of dumping syndrome.