Time progression from the patient's operating room entrance to incision: factors affecting anesthetic setup and surgical preparation times.

PURPOSE: Owing to recent advances in surgical technology, substantial time is required for preparing surgical equipment before incision. The purpose of this study was to demonstrate the time progression from a patient's operating room entrance to incision and to evaluate the duration of each anesthetic procedure and surgical preparation. METHODS: We marked the following seven points on the anesthetic chart: (1) entrance; (2) i.v. line placement; (3) preoxygenation; (4) intubation; (5) completion of patient positioning (Anesth-Set); (6) applying antiseptic solution; and (7) incision. Afterward, we analyzed the event time periods according to anesthetic procedure, patient position, surgical service, and surgical procedure (such as the utilization of endoscopy, navigation systems, and sentinel lymph node biopsy). RESULTS: On average, it took approximately 3 min to start i.v. placement, 7 min until preoxygenation, 15 min until intubation, and 30 min until Anesth-Set. Epidural, arterial, and central venous catheterization required 15, 9, and 13 min, respectively. It took 20 min from Anesth-Set to incision, on average; 22, 4, and 5 min were required to prepare the navigation system, endoscope, and sentinel lymph node biopsy, respectively. In total, it took an average of 49.8 +/- 17.1 min from entrance to incision, which was significantly longer (30.4 +/- 8.8 min) than it took in 1985-1986. CONCLUSION: The mean time taken from the patient's operating room entrance to incision is now significantly longer than before. This may be attributed, at least in part, to the preparation of equipment associated with new surgical technologies.

Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes.

The water channel protein aquaporin (AQP) may play roles in the homeostasis of water content in the brain and brain edema. One possible mechanism of brain edema is glial swelling due to lactic acidosis associated with ischemia. Here, we investigated the effect of lactic acid on the expression and cellular distribution of AQP 4 in cultured rat astrocytes. After 24h of incubation, the AQP4 expression level increased maximally with 35mM lactic acid. The AQP4 expression levels also increased with hydrochloric acid or acetic acid. In contrast, with sodium lactate, the AQP4 levels did not increase. The increase in AQP4 expression level occurred without a significant increase in AQP4 mRNA expression level by lactic acid. Under the conditions of de novo protein synthesis inhibition with cycloheximide, lactic acid increased the AQP4 expression level. Furthermore, lactic acid increased the AQP4 expression level on the cell surface of the astrocytes, as determined by a cell surface biotinylation assay and immunocytochemical examination. The increase in AQP4 expression level on the cell membrane of astrocytes induced by lactic acid may be a new regulation mechanism of AQP4 in the brain.

[Aquaporin water channels in the brain and molecular mechanisms of brain edema].

Aquaporins(AQPs) are a family of water selective channel. Transcripts of AQP1, AQP3, AQP4, AQP5, AQP8, and AQP9 are detected in the brain. Especially in astrocytes, AQP4 is abundantly expressed in end feet at the blood-brain barrier. Brain AQPs play important roles in the regulation of water homeostasis and the cerebro spinal fluid formation. Recently, AQP4 and AQP9 have been reported to involve in the brain water accumulation in the brain edema. Studies of transgenic mouse and brain injury models reveal that AQP4 may play a role not in the edema formation, but in the fluid elimination. Further study of AQPs functions in the brain may provide new insights into the brain edema and allow the design of novel anti edema medications.

Sensitive immunoassays for human and rat GMFB and GMFG, tissue distribution and age-related changes.

We developed sensitive and specific two-site enzyme immunoassays (EIA) for glia maturation factor beta (GMFB) and gamma (GMFG) using specific antibodies raised in rabbits. These assay systems enabled us to identify GMFB and GMFG (GMFs) in both human and rat samples and they were used to investigate the tissue distribution and serum concentrations of human and rat GMFs. In the case of rat, relatively high levels of GMFB were found in the central nervous system, except for the spinal cord, and in thymus and colon. Higher levels of GMFG were found in the thymus, spleen and colon. The distribution of GMFs in human was similar to that in rat. In the rat, the maximum serum concentration of GMFG was at 4 weeks of age. The decrease in its level was rapid for the first 30 days of life in both sexes. On the other hand, the concentration of GMFB in serum did not change significantly with age. Similarly, in human, the concentration of GMFG in serum was highest in the 21-30-year-old group and began to decrease rapidly in the 30-year-old group. In contrast, the concentration of GMFB did not change significantly during this period. No significant sex differences in the serum levels of GMFs were observed in human and rat. The present EIA systems are sufficiently sensitive for studying GMFs in human and rat organs.

Reduced hyperpolarization in endothelial cells of rabbit aortic valve following chronic nitroglycerine administration.

This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the hyperpolarization induced by acetylcholine (ACh) in aortic valve endothelial cells (AVECs) of the rabbit and, if so, whether antioxidant agents can normalize this downregulated hyperpolarization. ACh (0.03-3 microM) induced a hyperpolarization through activations of both apamin- and charybdotoxin-sensitive Ca2+-activated K+ channels (K(Ca)) in rabbit AVECs. The intermediate-conductance K(Ca) channel (IK(Ca)) activator 1-ethyl-2-benzimidazolinone (1-EBIO, 0.3 mM) induced a hyperpolarization of the same magnitude as ACh (3 microM). The ACh-induced hyperpolarization was significantly weaker, although the ACh-induced [Ca2+]i increase was unchanged, in NTG-treated rabbits (versus NTG-untreated control rabbits). The hyperpolarization induced by 1-EBIO was also weaker in NTG-treated rabbits. The reduced ACh-induced hyperpolarization seen in NTG-treated rabbits was not modified by in vitro application of the superoxide scavengers Mn-TBAP, tiron or ascorbate, but it was normalized when ascorbate was coadministered with NTG in vivo. Superoxide production within the endothelial cell (estimated by ethidium fluorescence) was increased in NTG-treated rabbits and this increased production was normalized by in vivo coadministration of ascorbate with the NTG. It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide.

Characteristics of attenuated endothelium-dependent relaxation seen in rabbit intrapulmonary vein following chronic nitroglycerine administration.

1 This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the endothelium-dependent relaxation induced by acetylcholine (ACh) in the rabbit intrapulmonary vein and, if so, whether the type 1 angiotensin II receptor (AT(1)R) blocker valsartan normalizes this downregulated relaxation. 2 In strips treated with the cyclooxygenase inhibitor diclofenac, ACh induced a relaxation only when the endothelium was intact. A small part of this ACh-induced relaxation was inhibited by coapplication of two Ca(2+)-activated K(+)-channel blockers (charybdotoxin (CTX)+apamin) and the greater part of the response was inhibited by the nitric-oxide-synthase inhibitor N(omega)-nitro-L-arginine (L-NNA). 3 The endothelium-dependent relaxation induced by ACh, but not the endothelium-independent relaxation induced by the nitric oxide donor NOC-7, was significantly reduced in NTG-treated rabbits (versus those in NTG-nontreated control rabbits). The attenuated relaxation was normalized by coapplication of valsartan with the NTG. 4 In the vascular wall, both the amount of localized angiotensin II and the production of superoxide anion were increased by in vivo NTG treatment. These variables were normalized by coapplication of valsartan with the NTG. 5 It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced endothelium-dependent relaxation, mainly through an inhibition of endothelial nitric oxide production in the rabbit intrapulmonary vein. A possible role for AT(1)R is proposed in the mechanism underlying this effect.

Differential regulation of aquaporin-5 and -9 expression in astrocytes by protein kinase A.

Aquaporins (AQPs) transport water through the membranes of numerous tissues, but the molecular mechanisms for regulating water balance in brain are unknown. In this study, we investigated the effects of a protein kinase A (PKA) activator on the expression of AQP4, 5 and 9 in cultured rat astrocytes. Treatment of the cells with dbcAMP caused decreases in AQP5 mRNA and protein and increases in AQP9 mRNA and protein in time- and concentration-dependent manners. However, AQP4 mRNA and protein were not changed by treatment with dbcAMP. The dbcAMP-induced effects on AQP5 and AQP9 mRNAs were inhibited by PKA inhibitors. In addition, pretreating the cells with an inhibitor of protein synthesis, cycloheximide, inhibited the increase in AQP9 mRNA induced by dbcAMP, but not the decrease in AQP5 mRNA. These results suggest that signal transduction via PKA may play important roles in regulating the expression of AQP5 and AQP9, and the effect on AQP9 may be mediated by some factors induced by dbcAMP.

A cross-cultural comparison of critical care delivery: Japan and the United States.

OBJECTIVE: To compare the utilization and outcomes of critical care services in a cohort of hospitals in the United States and Japan. DESIGN: Prospective data collection on 5,107 patients and detailed organizational characteristics from each of the participating Japanese study hospitals between 1993 and 1995, with comparisons made to prospectively collected data on the 17,440 patients included in the US APACHE (acute physiology and chronic health evaluation) III database. SETTING: Twenty-two Japanese and 40 US hospitals. PATIENTS: Consecutive, unselected patients from medical, surgical, and mixed medical/surgical ICUs. MEASUREMENTS: Severity of illness, predicted risk of in-hospital death, and ICU and hospital length of stay (LOS) were assessed using APACHE III. Japanese ICU directors completed a detailed survey describing their units. MAIN RESULTS: US and Japanese ICUs have a similar array of modalities available for care. Only 1.0% (range, 0.56 to 2.7%) of beds in Japanese hospitals were designated as ICUs. The organization of the Japanese and US ICUs varied by hospital, but Japanese ICUs were more likely to be organized to care for heterogeneous diagnostic populations. Sample case-mix differences reflect different disease prevalence. ICU utilization for women is significantly lower (35.5% vs 44.8% of patients) and there were relatively fewer patients > or = 85 years old in the Japanese ICU cohort (1.2% vs 4.6%), despite a higher per capita rate of individuals > or = 85 years old in Japan. The utilization of ICUs for patients at low risk of death significantly less in Japan (10.2%) than in the United States (12.9%). The APACHE III score stratified patient risk. Overall mortality was similar in both national samples after accounting for differences in hospital LOS, utilizing a model that was highly discriminating (receiver operating characteristic, 0.87) when applied to the Japanese sample. The application of a US-based mortality model to a Japanese sample overestimated mortality across all but the highest (> 90%) deciles of risk. Significant variation in expected performance was noted between hospitals. Risk-adjusted ICU LOS was not significantly longer in Japan; however, total hospital stay was nearly twice that found in the US hospitals, reflecting differences in hospital utilization philosophies. CONCLUSIONS: Similar high-technology critical care is available in both countries. Variations in ICU utilization reflect differences in case-mix and bed availability. Japanese ICU utilization by gender reflects differences in disease prevalence, whereas differences in utilization by age may reflect differences in cultural norms regarding the limits of care. Such differences provide context from which to assess the delivery of care across international borders. Miscalibration of predictive models applied to international data samples highlight the impact that differences in resource use and local practice cultures have on outcomes. Models may require modification in order to account for these differences. Nevertheless, with large databases, it is possible to assess critical care delivery systems between countries accounting for differences in case-mix, severity of illness, and cultural normative standards facilitating the design and management such systems.

Effect of mild hypothermia on the expression of aquaporin family in cultured rat astrocytes under hypoxic condition.

Aquaporins (AQPs) are a family of water-selective transporting proteins with homology to the major intrinsic protein (MIP) of lens, that increase plasma membrane water permeability in secretory and absorptive cells. In this study, we investigated the effect of mild hypothermia on the expression of AQP4, AQP5 and AQP9 in rat astrocytes cultured under hypoxic conditions. At 37 degrees C, a marked decrease in the expression of AQP4, AQP5 and AQP9 mRNAs was observed. However, at 32 degrees C (mild hypothermia), the expression of AQP5 mRNA was restored to its basal level. Interestingly, under mild hypothermia AQP4 mRNA expression transiently decreased and then increased about two-fold; while AQP9 mRNA expression decreased the same as at 37 degrees C. The changes in the expression of AQP4 and AQP9 proteins were confirmed by Western blot analysis. The restoration of the AQP4 and AQP5 expression at 32 degrees C from the hypoxia-induced decrease at 37 degrees C may play an important role in the reduction of brain edema under hypothermic conditions.

Effects of H2O2 on membrane potential of smooth muscle cells in rabbit mesenteric resistance artery.

The effects of H(2)O(2) on the membrane potential of smooth muscle cells of rabbit mesenteric resistance arteries were investigated. H(2)O(2) (3-30 microM) concentration-dependently hyperpolarized the membrane; this was inhibited by catalase but not by superoxide dismutase or the hydroxyl-radical scavenger dimethylthiourea. The cyclooxygenase inhibitor diclofenac partly inhibited the responses; the subsequent addition of the 5-lipoxygenase inhibitor 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone (AA-861) (but not the cytochrome P(450) inhibitor 17-octadecynoic acid) further attenuated H(2)O(2)-induced hyperpolarizations. The sarcolemmal ATP-sensitive K(+) (K(ATP)) channel inhibitor 1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenylsulfonyl]-3-methylthiourea, sodium salt (HMR-1098), blocked the H(2)O(2)-induced hyperpolarization in the absence and presence of diclofenac. H(2)O(2) increased the production of prostaglandin E(2) and prostacyclin (estimated from its stable metabolite 6-keto-prostaglandin F(1alpha)), both of which produce a HMR-1098-sensitive hyperpolarization in the smooth muscle cells. It is concluded that, in smooth muscle cells of rabbit mesenteric artery, H(2)O(2) increases the synthesis of vasodilator prostaglandins and possibly 5-lipoxygenase products, which produce a hyperpolarization by activating sarcolemmal K(ATP) channels.

Thermal properties of acid-induced depolarization in cultured rat small primary afferent neurons.

Tissue ischemia and inflammation result in localized acidosis, and acidic pH can trigger a sensation of pain. Pain is known to be often modified by the tissue temperature. The purpose of this study is to clarify the thermal behavior of nociceptors in response to acidification using intracellular recordings from cultured rat primary afferent neurons. Extracellular acidification induced depolarization of two types, transient and sustained responses. The former (to pH 6.3 and 5.2) was augmented at lower temperature (26, 16 degrees C) and amiloride blocked the response to pH 6.3 at 26 degrees C. On the other hand, the sustained depolarization, which often followed the transient one, in response to pH 6.3 was greater at 36 degrees C and significantly blocked by capsazepine at 36 degrees C, but not at 26 degrees C. The sustained response to pH 5.2 was blocked even at 26 degrees C. These results suggest that the low pH evoked depolarization is temperature-dependent, and the contribution of transient receptor potential V1 (vanilloid receptor 1) to proton-induced response is greater in the physiological body temperature range, while that of the acid-sensing-ion-channel family is greater at room temperature or lower.

[Evaluation of preoperative anxiety in patients with and without premedication].

BACKGROUND: The purpose of this investigation was to determine whether elimination of premedication before general anesthesia affects preoperative anxiety. METHODS: Subjects were assigned to one of two groups: a sedative group (0.5 mg midazolam i.m., n = 111) or a no-premedication group (n = 98). We used patients' responses to a questionnaire to compare the no-premedication group and the sedative group. RESULTS: Eighty-three percent of patients in the no-premedication group entered the operating room ambulatory. The responses concerning preoperative anxiety were not different between the two groups. There was a high rate of recall of the conversation before anesthesia induction in the no-premedication group, and most of these patients replied that making conversation before general anesthesia was beneficial to them. Increases in heart rate and blood pressure at the point of entrance to operating room were observed in the no-premedication group, but the degrees of increase were not considered clinically important. CONCLUSION: We conclude that elimination of premedication does not increase anxiety in comparison with patients receiving sedatives, but makes patients feel comfortable by way of preoperative conversation. Elimination of premedication also makes ambulatory entrance possible, both improving safety with respect to patient identification and reducing the demand on nursing.

[A comparison of perioperative factors with two methods of coronary artery bypass grafting (CABG): off-pump and conventional].

BACKGROUND: The safety and efficiency of off-pump coronary artery bypass grafting (OPCAB) are still controversial. The purpose of this study was to evaluate this approach in comparison with the conventional cardiopulmonary bypass technique (cCABG). METHODS: A retrospective review of patients who had undergone coronary artery bypass grafting independently without other operations between January 1, 1999 and September 30, 2001 was performed. The patients were divided into two groups: those who underwent OPCAB and the remainder for cCABG. The perioperative factors of the two groups were compared. RESULTS: A total of 152 OPCAB and 142 cCABG cases were reviewed. Compared with cCABG, OPCAB significantly reduced the amount of catecholamine needed on admission to ICU, intubation time, overall hospital length of stay, and neurologic events. There were also trends for decreases in ICU length of stay, mortality, and renal failure. On the other hand, OPCAB did not affect perioperative blood loss. CONCLUSIONS: Overall OPCAB is safer and more efficient than cCABG. However, we have to note in anesthetic management that OPCAB does not reduce blood loss.

Insulin-like growth factor-I reduces stress-induced gastric mucosal injury by inhibiting neutrophil activation in mice.

OBJECTIVE: We previously reported that activated neutrophils are critically involved in the development of stress-induced gastric mucosal injury in mice. Caspase activation plays an important role in the pathogenesis of tissue injury by activating neutrophils through an increase in the expression of endothelial monocyte-activating polypeptide-II (EMAP-II), a chemoattractant for neutrophils. Since insulin-like growth factor-I (IGF-I) inhibits caspase activation, it is possible that IGF-I reduces gastric mucosal injury by inhibiting neutrophil activation. In the present study, we examined this possibility in mice subjected to water-immersion restraint stress (WIR). DESIGN: Mice were intraperitoneally administered with IGF-I or vehicle before being subjected to WIR. Gastric mucosal injury, gastric myeloperoxidase (MPO) activity, the immunofluorescence intensity of MPO, caspase-3 activity, number of apoptotic cells, EMAP-II expression and activation of Akt and glycogen synthase kinase-3beta (GSK-3beta) in gastric mucosa were determined in mice subjected to WIR. Neutropenia was induced by administration of methotrexate (MTX). RESULTS: Administration of IGF-I at dosages higher than 200 microg/kg significantly reduced gastric mucosal injury and inhibited increases in gastric MPO activities after 8h of WIR. Administration of MTX also reduced the gastric mucosal injury as well as inhibiting increases in both gastric mucosal MPO activities and circulating neutrophil number. IGF-I (500 microg/kg) inhibited the increases in both gastric MPO activity and the immunofluorescence intensity of MPO observed in the gastric mucosa, but had no effect on the increase in circulating neutrophil number after 8h of WIR. It also markedly blunted WIR-induced increases in caspase-3 activities and the number of apoptotic cells in the gastric mucosa after 8h of WIR. Gastric expression of EMAP-II was markedly increased at 8h after starting WIR and this increase was inhibited by IGF-I administration. Administration of IGF-I enhanced WIR-induced phosphorylation of Akt and GSK-3beta in the gastric mucosa. CONCLUSION: These observations indicate that IGF-I reduces stress-induced gastric mucosal injury by inhibiting gastric accumulation of neutrophils through inhibition of caspase-3-mediated EMAP-II activation. Furthermore, IGF-I might inhibit caspase-3 activation through Akt/GSK-3beta signaling.

Orotracheal intubation with an AirWay Scope in a patient with Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is a congenital malformation of craniofacial development; in these patients conventional direct laryngoscopy is very difficult and often unsuccessful because of the upper airway malformation. A 20-year-old man with TCS was scheduled for elective tympanoplasty. The patient showed the characteristic facial appearance of TCS, and a difficult airway was anticipated. After careful anesthesia induction, direct laryngoscopy with Macintosh blade no. 4 of a direct laryngoscope failed to visualize the epiglottis, even with cricoid pressure, resulting in a grade 4 Cormack and Lehane view. Next, the AirWay Scope was easily inserted, and his glottic opening was clearly visualized. An 8.0-mm-internal-diameter tracheal tube was then advanced into the trachea without any difficulty. The AirWay Scope is a very useful airway device for orotracheal intubation; it provides an excellent view of the glottis without requiring alignment of the oral, pharyngeal, and laryngeal axes, and appears to be promising for use in patients with a difficult airway.

The skin-traction method increases the cross-sectional area of the internal jugular vein by increasing its anteroposterior diameter.

PURPOSE: We developed a novel "skin-traction method" in which the puncture point of the skin over the internal jugular vein (IJV) is stretched upward with several pieces of surgical tape in the cephalad and caudad directions to facilitate cannulation of the IJV. We investigated whether this method increases the cross-sectional area of the IJV. METHODS: In 11 healthy volunteers, the cross-sectional area, anteroposterior diameter, and transverse diameter of the right IJV (RIJV) were recorded by ultrasound echo at head tilts of +10 degrees , +5 degrees , 0 degrees , -5 degrees , and -10 degrees with and without the skin-traction method. RESULTS: The skin-traction method significantly increased the cross-sectional areas of the RIJV at head tilts of +10 degrees , +5 degrees , and 0 degrees . In the flat position, the skin-traction method increased the cross-sectional area of the RIJV from 1.21 +/- 0.44 cm(2) to 1.75 +/- 0.60 cm(2) (44.6% increase), which is almost the same as that in the Trendelenburg position without this method (1.60 +/- 0.54 cm(2) at -5 degrees and 1.83 +/- 0.56 cm(2) at -10 degrees ). The anteroposterior diameter of the RIJV was significantly increased in all positions with this method, although the transverse diameter was not. CONCLUSION: This method significantly increased the cross-sectional area of the RIJV by increasing the anteroposterior diameter of the RIJV. Even in the flat position, this method was almost as efficacious as the Trendelenburg position. This method thus appears to facilitate IJV cannulation.

Circulatory collapse caused by unnoticed hypermagnesemia in a hospitalized patient.

We report a case of hypermagnesemia in a hospitalized patient after prolonged laxative use; due to preexisting impaired consciousness and digestive problems, the hypermagnesemia was difficult to detect until it almost became fatal. A 64-year-old man who was a patient at another hospital for treatment of head injury and gastric ulcer had developed circulatory collapse and was transferred to our hospital. Hypermagnesemia (serum magnesium concentration 11.0 mg.dl(-1)) was thought to be the cause of the circulatory collapse and treatments were successful. A magnesium laxative had been administered for more than a month at the previous hospital, but the patient's serum magnesium level was never measured. Care should be taken when a magnesium laxative is administered to patients who already have impaired consciousness and digestive problems that are early symptoms of hypermagnesemia.

Cardiac output increases the rate of carbon monoxide elimination in hyperpneic but not normally ventilated dogs.

PURPOSE: The very high solubility of carbon monoxide (CO) in blood suggests that its elimination depends predominantly on ventilation and not perfusion. Nevertheless, hyperventilation is not used for CO elimination because of the adverse effects of hypocapnia. With isocapnic hyperpnea (IH), ventilation can be increased considerably without hypocapnia. This raises the issue of whether CO elimination is limited by perfusion during IH. We studied the effect of increasing cardiac output on t1/2, the half-time of decline of blood carboxyhemoglobin concentration ([COHb]), during normal ventilation (NV) and during IH. METHODS: After ethics approval was received, 13 pentobarbital-anesthetized ventilated dogs were exposed to CO to increase their [COHb]. They were then ventilated with NV or IH. At each level of ventilation, dogs were randomly assigned to treatment with dobutamine (to increase cardiac output) or to no dobutamine treatment. After the return of [COHb] to control levels, each dog was re-exposed to CO and treated with the same ventilatory mode, but the alternative inotropic treatment. RESULTS: Gas exchange, [COHb], and hemodynamic measures were recorded during the study. Cardiac index values in the IH group were 4.1 +/- 0.5 and 8.2 +/- 1.2 l.min(-1).m(-2) without and with dobutamine infusion, respectively. Dobutamine infusion was associated with a reduction in t1/2 from 20.3 +/- 3.6 to 16.9 +/- 2.4 min (P = 0.005) in the IH group, but no change in the NV group. CONCLUSION: These findings suggest that CO elimination during IH treatment is limited at least partly by pulmonary blood flow and may therefore be further augmented by increasing cardiac output.

Carvedilol, a nonselective beta-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro.

Tumor necrosis factor (TNF) and tissue factor (TF) produced by monocytes and macrophages have been shown to be among the aggravating factors for chronic heart failure (CHF), because they induce cardiac dysfunction and thrombotic complications, respectively. Carvedilol, a nonselective beta-adrenoceptor antagonist with alpha(1)- adrenoceptor blockade action, has been demonstrated to improve the outcome of patients with severe CHF, suggesting that carvedilol might inhibit the production of TNF and TF. In this study, this possibility is examined using isolated human monocytes stimulated with lipopolysaccharide (LPS) in vitro. Carvedilol (10 muM) significantly inhibited LPS-induced production of TNF and TF by monocytes, whereas prazosin (a selective alpha(1)-adrenoceptor antagonist), bisoprolol (a selective beta(1)-adrenoceptor antagonist), ICI-118,551 (a selective beta(2)-adrenoceptor antagonist), and arotinolol (a nonselective beta-adrenoceptor antagonist with alpha(1)-adrenoceptor blockade action) did not. Carvedilol inhibited both expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but it did not inhibit activation of either nuclear factor-kappaB or activator protein-1 in monocytes stimulated with LPS. These results suggest that carvedilol inhibits LPS-induced production of TNF and TF by inhibiting activation of the ERK1/2-Egr-1 pathway independent of its adrenoceptor inhibitory activities in monocytes.

Anesthetic management of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) during laparotomy.

A 53-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) underwent a gastrectomy. We administered bicarbonated Ringer's solution, which has a physiological concentration of bicarbonate. The level of serum lactate did not increase significantly, and metabolic acidosis did not occur throughout surgery or for 3 h after surgery. Aggressive warming was needed to maintain normothermia, presumably because the mitochondrial respiratory chain, which is responsible for thermogenesis, is impaired in MELAS patients. It is important to maintain normothermia in MELAS patients in order to avoid further mitochondrial metabolic depression.