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The aims of this study are (1) to assess the effects of volatile anesthetics on regional cerebral blood flow (rCBF) and electrocorticography (ECoG), and (2) to investigate the relationship between rCBF and ECoG influenced by volatile anesthetics. The authors measured rCBF using laser Doppler flowmetry and ECoG simultaneously and continuously from the same cortex during craniotomy, using the specially arranged probe. Patients received intravenous anesthetics with nitrous oxide until craniotomy, and after opening of dura, volatile anesthetic, either isoflurane or sevoflurane, was started and was gradually increased for the measurement. Four of the nine cases (44.4%) of the sevoflurane group showed no change both in rCBF and ECoG. In three cases (33.3%), rCBF increased as the frequency of the paroxysmal activities increased. In two cases (22.2%), decreased rCBF was accompanied by slow waves. In 12 cases of the isoflurane group, no apparent rCBF and ECoG changes were seen, except a case with decreased rCBF and slow waves. This is the first report of simultaneous recordings of regional CBF and neuronal activity under general anesthesia. During sevoflurane and isoflurane anesthesia 2.5 minimum alveolar anesthetic concentration, rCBF is affected by ECoG activities rather than pharmacologic action of inhala- tional anesthetics.

Aortocaval fistula is a rare complication of ruptured abdominal aortic aneurysm (AAA), and patients with an aortocaval fistula show multiple symptoms. We report an 87-year-old man who was diagnosed as having an AAA with aortocaval fistula and who developed refractory hypotension after induction of anesthesia. Following a phenylephrine injection for slight hypotension induced by anesthetic induction, he developed severe hypotension and bradycardia, and his skin became cyanotic. Vasopressor agents had no immediate effect on the hypotension, but blood pressure gradually increased in about 30 min with continuous infusion of dopamine and noradrenaline. Transesophageal echocardiography (TEE) showed right ventricle (RV) hypokinesis and massive tricuspid regurgitation (TR). Central venous pressure (CVP) showed a remarkably high value. After the repair of the aortocaval fistula, the hemodynamics became stable, RV motion was improved, TR was reduced, and CVP became normal. Anesthetic management of the repair of an aortocaval fistula is very difficult. The hemodynamics changed dramatically throughout anesthesia in our patient with this disorder, even though low-dose anesthetics were used. For the successful treatment of this disorder, preparation for the operation is required before the induction of anesthesia, and urgent closure of the fistula is necessary after the induction of anesthesia. TEE is a useful tool for monitoring hemodynamics in such patients.

Objective. The purpose of this study was to determine how well liver position, the lung area-to-head circumference (L/H) ratio, and the lung-to-thorax transverse area (L/T) ratio predicted the need for extracorporeal membrane oxygenation (ECMO) and survival in fetuses with isolated congenital diaphragmatic hernia (CDH). Methods. Antenatal records of 25 fetuses with isolated left-sided CDH who were born by cesarean delivery under fetal stabilization at this institution were reviewed. The latest determinations of the L/H and L/T ratios before birth (between 34 and 38 weeks’ gestation) were compared on the basis of the cutoff points for mortality: less than 1.0 versus 1.0 or greater for the L/H ratio and 0.08 or less versus greater than 0.08 for the L/T ratio. Outcome measures assessed were survival (discharge to home) and the need for ECMO. Results. Overall survival was 64% (16/25). Postnatal survival in fetuses with an L/T ratio of 0.08 or less was statistically lower than in those with an L/T ratio of greater than 0.08 (33% versus 81%; P = .0308). The percentage requiring ECMO in the group with an L/T ratio of 0.08 or less was also higher than that of the group with an L/T ratio of greater than 0.08, but the difference was not statistically significant (67% versus 25%; P = .0872). Neither the L/H ratio nor herniation of the fetal liver into the chest affected survival or the need for ECMO. Conclusions. In fetuses with isolated CDH at term or near term, the L/T ratio may be a better predictor of outcome than the L/H ratio or liver herniation. Key words: congenital diaphragmatic hernia; lung area-to-head circumference ratio; lung hypoplasia; lung-to-thorax transverse area ratio; sonography.

Background and purpose: Myosin light chain kinase (MLCK) plays a pivotal role in regulation of cellular functions, the evidence often relying on the effects of extracelluarly administered drugs such as ML-9. Here we report that this compound exerts non-specific inhibitory actions on the TRPC6 channel, a transient receptor potential (TRP) protein. Experimental approach: Macroscopic and single channel currents were recorded from transfected HEK293 cells by patch-clamp techniques. Key results: Cationic currents elicited by carbachol (CCh; 100 μM) in HEK293 cells overexpressing murine TRPC6 (ITRPC6) were dose-dependently inhibited by externally applied ML-9 (IC50=7.8 μM). This inhibition was voltage-dependent and occurred as fast as external Na+ removal. Another MLCK inhibitor, wortmannin (3 μM), and MLCK inhibitory peptides MLCK-IP11-19 (10 μM) and -IP480-501 (1 μM) showed little effects on ITRPC6 density and the inhibitory efficacy of ML-9. The extent of the inhibition also unchanged with co-expression of wild-type or a dominant negative mutant of MLCK. Inhibitory effects of ML-9 on ITRPC6 remained unaffected whether TRPC6 was activated constitutively or by a diacylglycerol analogue OAG (100 μM). Similar rapid inhibition was also observed with a ML-9 relative, ML-7. Intracellular perfusion of ML-9 via patch pipette, dose-dependently suppressed ITRPC6. In inside-out patch configuration, bath application of ML-9 (and ML-7) rapidly diminished ∼35pS single TRPC6 channel activities. Contrarily, currents due to TRPC7 expression were rapidly enhanced by externally applied ML-9 and ML-7, which was not prevented by MLCK inhibitory peptides. Conclusion and implications: These results strongly suggest that ML compounds inhibit TRPC6 channels via a mechanism independent of inhibition of MLCK activity. British Journal of Pharmacology (2007) 152, 122–131; doi:10.1038/sj.bjp.0707368

The purpose of this study was to examine and compare the four combination of pulse oximeters (POs) and monitoring sites, the Nihon Kohden BSS-9800 (N), the Masimo SET Radical (M), the Nellcor N550 D-25 (N-D) and the Nellcor N550 Max-Fast (N-MF) in patients with peripheral hypoperfusion.About 20 adult patients undergoing cardiac surgery using mild hypothermic cardiopulmonary bypass (CPB) were studied prospectively. PO sensors were applied on fingers in N, M and N-D, while on the forehead in N-MF.PO failure was defined as failure to show no SpO2 value or incorrect SpO2 values. PO failure occurred in 12 patients with N, ten patients with M, four patients with N-D and ten patients with N-MF, respectively (p0.05 N-D vs. N, M, N-MF). The duration of PO failure was 19 +/- 30% of aortic cross-clamping with N, 29 +/- 33% with M, 10 +/- 26% with N-D and 43 +/- 57% with N-MF, respectively (p0.05 N-D vs. M and N-MF).The results suggested that N-D is most useful among four combinations of POs and monitoring sites tested in this study for monitoring SpO2 during hypoperfusion. The superiority of N-MF during hypoperfusion was not evident in the present study.

Objective— Plasmin is a key enzyme in fibrinolysis. We attempted to determine the possible role of plasmin in the regulation of vascular tone, while also investigating the mechanism of plasmin-induced vasorelaxation. Methods and Results— In porcine coronary artery, plasmin induced an endothelium-dependent relaxation. This relaxing effect was mostly abolished by a proteinase inhibitor, a plasmin inhibitor, or a nitric oxide (NO) synthase inhibitor. The preceding stimulation with plasmin significantly inhibited the subsequent relaxation induced by thrombin but not that induced by proteinase-activated receptor-1–activating peptide. The relaxation induced by trypsin and substance P remained unaffected by the preceding plasmin stimulation. The pretreatment with plasmin, thrombin, or trypsin significantly attenuated the plasmin-induced relaxation. In porcine coronary artery endothelial cells (PCAECs) and human umbilical vein endothelial cells (HUVECs), plasmin induced a transient elevation in the cytosolic Ca 2+ concentrations ([Ca 2+ ] i ). The preceding stimulation with plasmin inhibited the subsequent [Ca 2+ ] i elevation induced by thrombin but not that induced by trypsin. In PCAECs, plasmin concentration-dependently induced NO production. Conclusions— The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor.

The purpose of this study was to noninvasively evaluate intraoperative left ventricular (LV) performance by an online pressure-area relationship using transesophageal echocardiography (TEE) and tonometry.In study 1, LV pressure with a micromanometer catheter, LV cross-sectional area with TEE, direct radial pressure, and tonometric arterial pressure were simultaneously recorded in 5 patients (10 measurements) undergoing cardiac surgery. End-systolic elastance (E'es) was determined from pressure-area loops during inferior vena caval (IVC) occlusion. In study 2, in 16 patients undergoing repair of abdominal aortic aneurysm, LV performance (E'es; effective arterial load, E'a, and LV end-diastolic area, LV-EDA) was examined by noninvasive assessment of pressure-area loops using TEE and tonometry at aortic cross-clamping and unclamping.E'es by tonometric arterial pressure closely correlated with E'es by LV pressure (r = 0.92) in study 1. E'es at aortic clamping were not significantly different from those at unclamping. The clamping increased LV-EDA and E'a by approximately 13% and 44%, and the unclamping significantly decreased by 9% and 22%, respectively.Our results demonstrated that online tonometric arterial pressure and LV area measured by automated border detection (ABD) of TEE might be used to calculate E'es to estimate LV contractility and allow the estimation of LV performance during aortic clamping and unclamping.

Proteolysis plays an important role in inactivating protease-activated receptor-1 (PAR1). We aimed to determine the cleavage site(s) responsive for the proteolytic inactivation of PAR1 in human umbilical vein endothelial cells. Fura-2 fluorometry revealed that the preceding stimulation with trypsin abolished the subsequent [Ca(2+)](i) response to thrombin, while the responses to PAR1-activating peptides remained intact. On the other hand, thrombin had no effect on the subsequent response to trypsin. The immunostaining with antibodies against the residues 35-46 (SPAN12) and 51-64 (WEDE15) revealed the broad boundaries of cleavage. Trypsin removed both epitopes from the cell surface within 3 min, while thrombin removed the epitope of SPAN12. The longer incubation with thrombin removed the epitope of WEDE15. However, PAR1-activating peptides thereafter induced an attenuated but significant elevation of [Ca(2+)](i). Not only the receptor internalization as observed with a confocal microscope, but also an additional cleavage was thus suggested to contribute to the thrombin-induced removal of the epitope of WEDE15. The analyses of the PAR1 mutants identified three cleavage sites for trypsin; residues 41-42, 70-71 and 82-83. The cleavage at the latter two sites was suggested to dominate that at the former, and thus remove the ligand region (residues 42-47). The inactivation of PAR1 due to proteolytic removal of the ligand region may contribute not only to the inactivation of PAR1 by proteases such as trypsin, but also to the termination of the intracellular signaling initiated by thrombin in the vascular endothelial cells.

九州大学医学部では1995年から高機能患者シミュレータを導入し, 医学生に対する麻酔科蘇生科のベッドサイド実習で利用している. 患者を対象とする臨床実習の前後に, 学生グループが自ら立てた計画に基づき, 麻酔シミュレーションを実践する. 酸素投与や換気補助をしないまま麻酔導入したりすることも少なくない. 疑似医行為の結果を目の当たりにすることで, 医学生らは自らの臨床能力の程度を自覚し, また医行為のもつ危険性も身をもって理解する. 高機能患者シミュレーションは, 患者に負荷を一切かけることなく, 医学生たちが, 主体的に修練する動機付けを得る意義があると考える. その効果的な運用についてはさらなる検討が望まれる.

Objectives The authors aimed to establish a technique for quantitative analysis of regional wall motion abnormality (RWMA) using color kinesis (CK) of transesophageal echocardiography (TEE) in surgical patients. This technique was used to determine whether RWMAs develop de novo after infrarenal aortic cross-clamping in patients undergoing vascular surgery with a preoperative dipyridamole thallium stress test (DTST). Design An observational study. Setting University hospital. Participants Thirty-eight patients undergoing infrarenal abdominal aortic aneurysm resection or aortofemoral bypass. Measurements and main results CK images of the left ventricle (LV) were obtained from the midventricular transgastric short-axis view before and after infrarenal aortic cross-clamping using TEE and analyzed off-line using custom software. The predictive value of the category “reversible perfusion defect” (RD) was also estimated from DTST for predicting new RWMAs with CK. CK analysis is suitable for clinical use based on the comparison with conventional two-dimensional echocardiogram measurements and interobserver variability. CK analysis showed all 7 patients with persistent perfusion defects on DTST had RWMAs. New RWMAs occurred in 2 of 9 patients with RD and in 2 of 15 patients with normal DTST, indicating that there was no significant difference between RD and normal DTST in the incidence of new RWMAs. Conclusions A new method is available for clinical use, which is capable of visualizing RWMAs. These results suggest that new RWMAs introduced by aortic cross-clamping occur irrespective of the risk as assessed by preoperative DTST. CK with the new analysis method might be a useful tool to quantitatively evaluate RWMAs during surgery.

Intracellular signaling pathway mediated by small GTPase Rho and its effector Rho-kinase plays an important role in regulation of vascular smooth muscle contraction and other cellular functions. We have recently demonstrated that Rho-kinase is substantially involved in angiotensin II-induced gene expressions and various cellular responses in vitro. However, it remains to be examined whether Rho-kinase is involved in the angiotensin II-induced cardiovascular hypertrophy in vivo and, if so, what mechanisms are involved. Long-term infusion of angiotensin II for 4 weeks caused hypertrophic changes of vascular smooth muscle and cardiomyocytes in rats. Both changes were significantly suppressed by concomitant oral treatment with fasudil, which is metabolized to a specific Rho-kinase inhibitor, hydroxyfasudil, after oral administration. Angiotensin II caused a perivascular accumulation of macrophages and Rho-kinase activation, both of which were also significantly suppressed by fasudil. Vascular NAD(P)H oxidase expression (nox1, nox4, gp91phox, and p22phox) and endothelial production of superoxide anions were markedly increased by angiotensin II, both of which were also significantly suppressed by fasudil. Thus, fasudil ameliorated the impaired endothelium-dependent relaxations caused by angiotensin II without affecting vasodilator function of vascular smooth muscle. These results provide evidence that Rho-kinase is substantially involved in the angiotensin II-induced cardiovascular hypertrophy in rats in vivo. The suppression of endothelial NAD(P)H oxidase upregulation and resultant superoxide production and the amelioration of endothelial vasodilator function may be involved in this process. (Circ Res. 2003;93:767-775.)

Using fura-2 fluorometry of [Ca2+]i in response to thrombin, trypsin and protease-activated receptor activating peptides (PAR-APs), we determined whether trypsin cleaves protease-activated receptor 1 (PAR1) and activates it in the endothelial cells of the porcine aortic valves and human umbilical vein. Once stimulated with thrombin, the subsequent application of trypsin induced a [Ca2+]i elevation similar to that obtained without the preceding stimulation with thrombin in the valvular endothelial cells. However, the preceding stimulation with trypsin abolished the subsequent response to thrombin, but not to bradykinin or substance P. The response to PAR1-AP (SFLLRNP) was significantly (P

Kinins locally synthesized in the cardiovascular tissue are believed to contribute to the regulation of cardiovascular homeostasis by stimulating the endothelial cells to release nitric oxide, prostacyclin, or a hyperpolarizing factor via autocrine-paracrine mechanisms. This study was designed to investigate the action of sevoflurane on bradykinin-induced Ca2+ mobilization in endothelial cells in situ. Utilizing fura-2-loaded rat pulmonary arterial valve leaflets, the effects of sevoflurane were examined on bradykinin-induced increases in intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells in situ. In the presence of extracellular Ca2+ (1.5 mM), bradykinin (3-30 microM) produced an initial phasic and a subsequent tonic increase in [Ca2+]i in a concentration-dependent manner. However, it produced only the phasic increase in [Ca2+]i in the absence of extracellular Ca2+. Sevoflurane (5%, 0.67 mM) inhibited both the phasic and tonic responses to bradykinin. In these experiments, sevoflurane (3-5%) generated sustained increases (approximately 20-40% of the bradykinin-induced maximal increase in [Ca2+]i) in the resting [Ca2+]i level. Sevoflurane still increased [Ca2+]i after depletion of the intracellular Ca stores with ionomycin (0.1 microM ). However, the sevoflurane-induced increase in [Ca2+]i was eliminated by removal of the extracellular Ca and attenuated by NiCl (1-3 mM). In conclusion, in the pulmonary arterial valvular endothelial cells, sevoflurane inhibits both bradykinin-induced Ca2+ release from the intracellular stores and bradykinin-induced plasmalemmal Ca2+ influx. In addition, sevoflurane appears to stimulate the plasmalemmal Ca2+ influx and thereby increase the endothelial [Ca2+]i level. Sevoflurane might influence the pulmonary vascular tone through its direct action on the pulmonary arterial valvular endothelial cells.

Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload. D-glucose overload (23 mM) induced an accumulation of superoxide anion (O2−), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 μU ml−1 xanthine oxidase (XO) and 100 μM xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 μM, whereas much higher concentrations of propofol were required to scavenge O2− generated by 250 μU ml−1 XO and 100 μM xanthine (IC50: 13.5 μM). D-glucose overload attenuated ATP-induced NO production which was detected using diaminofluorescence-2 (DAF-2). The inhibition was reversed by propofol with an EC50 of 0.60 μM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 μM). D-glucose overload suppressed ATP-induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2− was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 μM, respectively. D-glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 μM propofol reduced this increase to 2.8 fold. We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+-dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2− accumulation, and involves, at least in part, the inhibition of cellular glucose uptake. British Journal of Pharmacology (2002) 137, 683–691. doi:10.1038/sj.bjp.0704912

Summary: To compare the neuroexcitatory effects of sevoflurane and isoflurane, we recorded electrocorticograms (ECoG) during wakefulness and during sevoflurane and isoflurane anesthesia in six patients with temporal lobe epilepsy (TLE). These patients had subdural grid electrodes chronically implanted in the temporal region. During sevoflurane anesthesia at 1.5 minimum alveolar concentration (MAC) of the combination with 67% nitrous oxide (N2O), a marked increase in interictal paroxysmal activities was observed in four patients. Two patients had a slight increase in paroxysmal activities. Activated areas were widely distributed, not being confined to the ictal onset zone of spontaneous seizures. However, isoflurane anesthesia at 1.5 MAC of the combination with 67% N2O was associated with less increased paroxysmal activity. While the neuroexcitatory properties of sevoflurane proved greater than those of isoflurane, the widespread irritative response to sevoflurane administration was not helpful in localizing the epileptogenic area.

The systemic administration of lipopolysaccharide (LPS), an experimental model of systemic bacterial infection is known to modulate nociception. It increases the prostaglandin E(2) (PGE(2)) levels in the preoptic area of the hypothalamus (POA) and the microinjection of PGE(2) into the POA and the neighboring basal forebrain induces hyperalgesia. We, therefore, hypothesized that the PGE(2) synthesized in these regions mediates intravenous (i.v.) LPS-induced hyperalgesia. To test this hypothesis, we microinjected cyclooxygenase (COX) inhibitors into several sites in the rat hypothalamus and observed their effects on the LPS (0.1-100 microg/kg, i.v.)-induced changes in nociceptive behavior as assessed by a plantar test. LPS (10 and 100 microg/kg, i.v.) reduced the paw-withdrawal latency at 90 min and 45-60 min after injection, respectively, both thus indicating a hyperalgesic effect. This hyperalgesia was observed only in the period before the development of fever which started 120-135 min after the LPS injection. The LPS (100 microg/kg, i.v.)-induced hyperalgesia was completely abolished by pretreatment with the microinjection of diclofenac (an inhibitor of COX-1 and 2) at 1.0 ng into the bilateral POA. Furthermore, it was also blocked by the microinjection of NS-398 (a selective COX-2 inhibitor) at 1.0 ng into the bilateral POA and the horizontal limb of the diagonal band of Broca (DBB), but not the lateral hypothalamic area, the paraventricular hypothalamic nucleus, and the ventromedial hypothalamic nucleus. These findings suggest that LPS (i.v.)-induced hyperalgesia is mediated predominantly through a COX-2 induced prostanoids in the POA and the DBB in rats.

To investigate the mechanism underlying the trypsin-induced endothelium-dependent relaxation, cytosolic Ca2+ concentration ([Ca2+]i) and tension development of smooth muscle were simultaneously monitored in the porcine coronary artery, and [Ca2+]i of in situ endothelial cells were monitored in the porcine aortic valvular strips, using fura-2 fluorometry. During the contraction induced by 30 nM U46619, a thromboxane A2 analogue, 100 nM trypsin induced a rapid transient significant decrease in both [Ca2+]i (from 67.9±5.1 to 15.7±4.4%) and tension (from 97.5±9.2 to 16.8±3.5%) of smooth muscle only in the presence of endothelium (100% level was assigned to the level obtained with the 118 mM K+-induced contraction). [Ca2+]i and the tension thus returned to the levels prior to the application of trypsin by 5 and 10 min, respectively. The initial phase of this relaxation was partly inhibited by 100 μM Nω-nitro-L-arginine (L-NOARG), and was completely inhibited by L-NOARG plus 40 mM K+ or L-NOARG plus 100 nM charybdotoxin and 100 nM apamin, while the late phase of the relaxation was inhibited by L-NOARG alone. Trypsin induced a transient [Ca2+]i elevation in the endothelial cells mainly due to the Ca2+ release from the intracellular stores, at the concentrations (1 – 100 nM) similar to those required to induce relaxation. In conclusion, trypsin induced an elevation in [Ca2+]i mainly due to Ca2+ release in endothelial cells, and thereby caused endothelium-dependent relaxation. The early phase of relaxation was due to nitric oxide and hyperpolarizing factors, while the late phase was mainly due to nitric oxide in the porcine coronary artery. British Journal of Pharmacology (2001) 134, 815–826; doi:10.1038/sj.bjp.0704318

Objective: To investigate the usefulness of low-dose milrinone on gastric intramucosal pH (pHi) and systemic inflammation in patients undergoing hypothermic cardiopulmonary bypass (CPB). Design: Prospective randomized study. Setting: University hospital. Participants: Twenty patients scheduled for cardiac surgery. Interventions: Ten patients were administered a low dose of milrinone, 0.25 μg/kg/min, from the initiation of CPB to 1 hour after admission to the intensive care unit. The other patients were administered saline. Supplemental inotropes and intravenous fluid were given to obtain adequate mean arterial blood pressure and pulmonary artery occlusion pressure. Measurements and Main Results: Gastric pHi and carbon dioxide pressure (PCO2) were assessed by capnometric air tonometry. The difference between PCO2 and arterial carbon dioxide pressure (PaCO2), PCO2-gap, was also examined. Systemic inflammatory responses were evaluated by serum interleukin-6 and leukocyte counts. Hemodynamics, oxygen delivery index, and oxygen uptake index were monitored with catheters in the radial and pulmonary arteries (thermodilution). The hepatic venous blood flow and left ventricular flow were measured using transesophageal echocardiography. Milrinone prevented gastric intramucosal acidosis, detected as a decrease in pHi or an increase in PCO2-gap, without affecting hepatic venous blood flow. Increases in interleukin-6, leukocyte count, and oxygen uptake index, all of which developed after CPB, were significantly less in the milrinone group than in the control group. Conclusion: These results suggest that in patients undergoing hypothermic CPB, supplemental low-dose milrinone prevents gastric intramucosal acidosis and increases in some markers of systemic inflammation. Copyright © 2001 by W.B. Saunders Company

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome can occur at any time in the course of pregnancy and is associated with many complications including fatal stroke. A 37-year-old female presented with HELLP syndrome causing an intracerebral hematoma, which was treated by evacuation and mild hypothermia. Unexpected diffuse cerebral swelling occurred on the 15th day of the initially favorable postoperative course. Considerable impairment of consciousness persisted despite conservative therapy. Serial computed tomographic findings indicated delayed cerebral vasospasm as the cause of the swelling. Particularly careful management is required even beyond the first 2 weeks for patients with stroke as a complication of HELLP syndrome.

1. An unsaturated fatty acid, leukotriene C(4) (LTC(4)), has a potent contractile effect on human airway smooth muscle, and has been implicated in the pathogenesis of human asthma. Using front-surface fluorometry with fura-PE3, the effect of LTC(4) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were investigated in porcine tracheal smooth muscle strips. 2. The application of LTC(4) induced little or no contraction despite a small and transient increase in [Ca(2+)](i). In the presence of LTC(4), however, the contractions evoked by high K(+) depolarization or a low concentration of carbachol (CCh) were markedly enhanced without inducing any changes in the [Ca(2+)](i) levels, thus indicating that LTC(4) increases the Ca(2+) responsiveness of the contractile apparatus. This LTC(4)-induced increase in Ca(2+) responsiveness could partly be reproduced in the permeabilized preparation of tracheal smooth muscle strips. 3. The LTC(4)-induced enhancement of contraction was accompanied by an increase in myosin light chain (MLC) phosphorylation and was blocked by a rho kinase inhibitor (Y-27632), but not by either a PKC inhibitor (calphostin C) or a tyrosine kinase inhibitor (genistein). 4. These results indicated that, in porcine tracheal smooth muscle, LTC(4) enhances the contraction by increasing the Ca(2+) responsiveness of the contractile apparatus in a MLC phosphorylation dependent manner, possibly through the activation of the rho-rho kinase pathway.

Using a method employing front-surface fura-2 fluorometry to measure the cytosolic Ca2+ concentration, [Ca2+]i, the mechanism of endothelium-dependent regulation of vascular tone by thrombin was studied in porcine renal interlobar arterial strips. At concentrations lower than 3 u ml−1, thrombin evoked only early transient relaxation, while at 3 u ml−1 and higher concentrations, thrombin caused an early relaxation and a subsequent transient contraction. Both thrombin-induced relaxation and contraction were abolished by removing the endothelium. Similar biphasic responses were observed with a protease-activated receptor-1-activating peptide. Early relaxation was associated with a decrease in [Ca2+]i, while the transient contraction was not associated with a change in [Ca2+]i of smooth muscle cells. A thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10−5 M ONO-3708) completely inhibited the thrombin-induced contraction, whereas a thromboxane A2 synthase inhibitor (10−5 M OKY-046) only partly inhibited it. When the thrombin-induced contraction was inhibited by ONO-3708, either pretreatment with Nω-nitro-L-arginine methylester (L-NAME) or an increase in the amount of external K+ to 40 mM did not abolish thrombin-induced relaxation during phenylephrine-induced sustained contraction. However, the combination of pretreatment with L-NAME and an elevation of external K+ to 40 mM completely abolished the relaxation. There was no significant difference in the concentration-dependent effects of thrombin on the initial early relaxation between conditions in which the contractile components either were or were not inhibited. Thrombin is thus considered to mainly activate protease-activated receptor-1 and cause a biphasic response, early relaxation and a transient contraction, in the porcine renal interlobar artery in an endothelium-dependent manner. The thrombin-induced endothelium-dependent relaxation was mediated by nitric oxide and hyperpolarizing factors, while the contraction was mediated by TXA2 and PGH2. British Journal of Pharmacology (2000) 131, 1635–1642; doi:10.1038/sj.bjp.0703737

More than 50% of patients suffer neuropsychologic impairment after cardiac surgery. We measured neuron-specific enolase (NSE) and S-100 protein (S-100) in patients' serum as putative markers of neuronal and astroglial cell injury, respectively. Group I (n = 13) underwent coronary artery bypass grafting (CABG) with mild hypothermic cardiopulmonary bypass (CPB); Group II (n = 6) underwent aortic arch replacement with deep hypothermic CPB; Group III (n = 8) underwent CABG under normothermia without CPB. During and after the operation, serum levels of NSE and S-100 were significantly increased only in Groups I and II (during CPB), NSE still being increased 12 h after surgery in Group II. This suggests that neuronal and astroglial cell injuries are more likely in patients undergoing CABG with mild hypothermic CPB or aortic arch replacement with deep hypothermic CPB than in those undergoing CABG under normothermia without CPB. However, these increases of NSE and S-100 failed to reflect clinical brain damage. Rather, an electroencephalogram, was only capable of detecting neurologic complications after surgery.Neuronal and astroglial cell injuries are likely to occur during coronary artery bypass grafting with mild hypothermic cardiopulmonary bypass (CPB) or aortic arch replacement with deep hypothermic CPB. Conversely, patients undergoing coronary artery bypass grafting without CPB under normothermic conditions may be less likely to suffer brain cell injury.

Background The direct action of sevoflurane on systemic resistance arteries is not fully understood. Methods Isometric force was recorded in isolated rat small mesenteric arteries. Results Sevoflurane (2-5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevoflurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), angiotensin-II, or sevotonin receptors. Sevoflurane (3-5%) inhibited contractile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, inhibition of the norepinephrine response, which was enhanced during application of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibition of norepinephrine response was similarly prolonged after washout of sevoflurane. However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact and the endothelium-denuded strips. Conclusions The action of sevoflurane on norepinephrine contractile response consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the norepinephrine response. The endothelium-independent component persisted after washout of sevoflurane, leading to prolonged inhibition of the norepinephrine response. The mechanisms behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium chloride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, and serotonin are not involved in the vasoconstricting action. (Key words: Halogenated volatile anesthetics; sympathetic nervous system; systemic hypotension; vascular endothelium.)

Background —We recently demonstrated that the Rho-kinase–mediated pathway plays an important role for coronary artery spasm in our porcine model with interleukin-1β (IL-1β). In this study, we examined whether or not Rho-kinase is upregulated at the spastic site and if so, how it induces vascular smooth muscle hypercontraction. Methods and Results —Segments of the left porcine coronary artery were chronically treated from the adventitia with IL-1β–bound microbeads. Two weeks after the operation, as reported previously, intracoronary serotonin repeatedly induced coronary hypercontractions at the IL-1β–treated site both in vivo and in vitro, which were markedly inhibited by Y-27632, one of the specific inhibitors of Rho-kinase. Reverse transcription–polymerase chain reaction analysis demonstrated that the expression of Rho-kinase mRNA was significantly increased in the spastic compared with the control segment. Western blot analysis showed that during the serotonin-induced contractions, the extent of phosphorylation of the myosin-binding subunit of myosin phosphatase (MBS), one of the major substrates of Rho-kinase, was significantly greater in the spastic than in the control segment and that the increase in MBS phosphorylations was also markedly inhibited by Y-27632. There was a highly significant correlation between the extent of MBS phosphorylations and that of contractions. Conclusions —These results indicate that Rho-kinase is upregulated at the spastic site and plays a key role in inducing vascular smooth muscle hypercontraction by inhibiting myosin phosphatase through the phosphorylation of MBS in our porcine model.

To present a case of massive retroperitoneal hemorrhage during cardiopulmonary bypass (CPB) which was detected using transesophageal echocardiography (TEE).A 50-yr-old man suffering from severe mitral regurgitation (MR) was admitted for mitral valvuloplasty. After the beginning of CPB, the volume in the reservoir was noticed to be gradually decreasing. Although venous cannulation had been properly performed, TEE showed an echo free space around the liver, the spleen and in front of the abdominal aorta showed intraabdominal hemorrhage. After cardiac surgery, emergency laparotomy revealed about 5,000 ml of blood in the retroperitoneal space probably as a result of femoral artery cannulation prior to CPB. Hemostasis was achieved, and the patient made complete cardiac and neurological recovery. Retrospective review of the TEE imaging revealed that the kidneys were surrounded by blood bilaterally confirming the diagnosis of retroperitoneal hemorrhage.Retroperitoneal hemorrhage during CPB is rare, but may be lethal. Transesophageal echocardiography is a useful monitor not only to evaluate cardiac performance, but also to detect unexpected intraabdominal bleeding during cardiac surgery.

Background Venodilation is thought to be one of the mechanisms underlying propofol-induced hypotension. The purpose of this study is to test two hypotheses: (1) propofol increases systemic vascular capacitance, and (2) the capacitance change produced by propofol is a result of an inhibition of sympathetic vasoconstrictor activity. Methods In 33 Wistar rats previously anesthetized with urethane and ketamine, vascular capacitance was examined before and after propofol infusion by measuring mean circulatory filling pressure (Pmcf). The Pmcf was measured during a brief period of circulatory arrest produced by inflating an indwelling balloon in the right atrium. Rats were assigned into four groups: an intact group, a sympathetic nervous system (SNS)-block group produced by hexamethonium infusion, a SNS-block + noradrenaline (NA) group, and a hypovolemic group. The Pmcf was measured at a control state and 2 min after a bolus administration of 2, 10, and 20 mg/kg of propofol. Results The mean arterial pressure (MAP) was decreased by propofol dose-dependently in intact, hypovolemic, and SNS-block groups, but the decrease in MAP was less in the SNS-block group (-25%) than in the intact (-50%) and hypovolemic (-61%) groups. In the SNS-block + NA group, MAP decreased only at 20 mg/kg of propofol (-18%). The Pmcf decreased in intact and hypovolemic groups in a dose-dependent fashion but was unchanged in the SNS-block and SNS-block + NA groups. Conclusions The results have provided two principal findings: (1) propofol decreases Pmcf dose-dependently, and (2) the decrease in Pmcf by propofol is elicited only when the sympathetic nervous system is intact, suggesting that propofol increases systemic vascular capacitance as a result of an inhibition of sympathetic nervous system.

To investigate changes in both core and peripheral skin-surface temperatures during and after application of a unilateral leg pneumatic tourniquet in adult patients.Prospective, observational clinical study.University hospital.21 ASA physical status I and II adult patients scheduled for elective leg orthopedic surgery with lumbar epidural anesthesia.Rectal and fingertip skin-surface temperatures were recorded every minute after steady-state lumbar epidural anesthesia was established.Significant (p0.05) increases in both rectal and fingertip temperatures were observed during tourniquet application for 91 +/- 6 minutes from 36.5 +/- 0.14 degrees C to 37.0 +/- 0.17 degrees C and from 32.6 +/- 0.79 degrees C to 35.5 +/- 0.44 degrees C, respectively. In contrast, both rectal and fingertip temperatures progressively decreased following tourniquet release; significant (p0.05) decreases in the rectal and fingertip temperatures were observed 6 and 5 minutes after tourniquet release, respectively. Decreases (approximately maximum) in the rectal and fingertip temperatures 15 minutes after tourniquet release were 0.25 +/- 0.05 degrees C and 1.26 +/- 0.26 degrees C, respectively. In each case, changes in fingertip temperature were approximately six times greater than those in the rectal temperature.Limb tourniquets appear to cause thermal perturbations during epidural anesthesia. The progressive increases in core temperature during tourniquet application presumably resulted from constraint of metabolic heat to the core thermal compartment, and the greater increases in the skin-surface temperature during tourniquet application appear to represent vasodilation in response to the core hyperthermia. On the other hand, redistribution of body heat and the efflux of hypothermic venous blood from the tourniqueted area into systemic circulation following tourniquet deflation probably decreased the core temperature, which might switch off the thermoregulatory vasodilation, leading to the decreases in skin-surface temperature. Recognition of these thermal perturbations are useful in diagnosing intraoperative thermal perturbations.

Endothelins (ETs) can modulate the airway smooth muscle tone. Using simultaneous measurements of cytosolic Ca2+ concentration ([Ca2+]i) and tension as well as the reverse transcription polymerase chain reaction (RT-PCR), we examined ET systems in the porcine trachea. In the functional study, the application of ET-1, ET-3 or sarafotoxin S6c (S6c) caused increases in [Ca2+]i and tension, in a concentration-dependent manner. These ET ligands were found to increase the Ca2+ sensitivity of the myofilament of the tracheal smooth muscle cells (SMCs). The contractions induced by ET-1 (10(-7) M), an ET receptor (ET-R) non-selective agonist, were much greater than those induced by S6c, an ET(B)-R selective agonist. BQ-123 (10(-6) M), an ET(A)-R antagonist, inhibited the ET-1 induced contraction. These functional experiments suggested the presence of both functioning ET(A)- and ET(B)-Rs in tracheal SMCs. RT-PCR experiments revealed that the tracheal SMCs expressed both ET(A)-R and ET(B)-R mRNAs, while tracheal epithelial cells (EpCs) predominantly expressed ET(A)-R mRNA. The porcine tracheal SMCs and EpCs also expressed pre-pro ET-1 (ppET-1), ppET-3, and endothelin converting enzyme-1 (ECE-1) mRNAs. These results suggested that ETs induce contraction of porcine tracheal SMCs not only by increasing [Ca2+]i but also increasing the Ca2+ sensitivity of the myofilament and that ETs could potentially be the autocrine and/or paracrine transmitters to regulate the contraction in the porcine airway smooth muscle.

Kinetics of immunological parameters such as natural killer (NK) cell activity and tritium-thymidine uptake rate of T lymphocytes by phytohemagglutinin stimulation were investigated using peripheral leukocyte fractions of melanoma patients treated with hyperthermic isolated limb perfusion (HILP). Also, serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were quantified during and after HILP. It was found that NK cell activity was augmented during HILP, and T lymphocyte function was stimulated 24 h and 1 week after HILP with statistical significance. NK cell activities in the cells isolated from perfused and non-perfused circulations were equally augmented during HILP in two patients examined. Serum concentrations of sICAM-1 in the patients who received HILP also increased 24 h or even 1 week after HILP. The stimulation of these immune competent cells and upregulation of sICAM-1 by HILP were independent of the stages of melanoma patients at the time of HILP or the doses of agents which were used for the infusion during HILP. The origin of cells which shed sICAM-1 into the serum of the patients who received HILP remains to be further investigated.

The purpose of this study was to examine the effects of nicardipine and sodium nitroprusside (SNP) on vascular capacitance in the rat. In ten rats anesthetized with pentobarbital, mean arterial pressure was lowered to about 70 mmHg and subsequently 50 mmHg by intravenous infusion of nicardipine or SNP. Vascular capacitance was assessed before and during nicardipine- or SNP-induced hypotension by measuring the mean circulatory filling pressure (MCFP). MCFP was measured during a brief period of circulatory arrest produced by inflating a balloon inserted in the right atrium. MCFP was significantly decreased by SNP from 7.1 ±0.3 mmHg at control to 5.6 ± 0.4 mmHg and 4.4 ± 0.3 mmHg at mean arterial pressures of 70 mmHg and 50 mmHg, respectively. However, MCFP stayed at a similar level to that of the control during nicardipine-induced hypotension. These results suggest that nicardipine has a negligible influence on vascular capacitance during induced hypotension, whereas SNP has a potent vasodilating effect on the venous system as well as the arterial system.

It has been reported that vasodilatory prostaglandins have cytoprotective effects against various types of liver damage. We investigated the effects OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats. Intraperitoneal administration of OP 2507 at 1,500 micrograms/kg lessened both an increase in serum alanine aminotransferase activity and an inhibition of starvation ketosis, both of which were induced by carbon tetrachloride. At lower doses, however, OP 2507 not only failed to ameliorate the carbon tetrachloride-induced changes, but it actually exaggerated them. Although the deterioration of carbon tetrachloride-induced liver damage by lower doses of OP 2507 was not statistically significant, it seems possible that OP 2507 has dual effects on carbon tetrachloride-induced liver damage. While none of the three agents cimetidine, reduced glutathione and deferoxamine, prevented increase in serum alanine aminotransferase activity induced with lower dose OP 2507, allopurinol had a tendency to prevent the increase, indicating that lower doses of OP 2507 may promote a reaction catalyzed by xanthine oxidase. We propose that both the co-administration of prostaglandins and other potentially hepatotoxic drugs, and the administration of prostaglandins to patients with drug-induced liver damage should be done carefully.

顔面痛はいろいろなメカニズムによって生じる.難治性の顔面痛を訴えた22歳の女性に,左茎状突起の過長と骨折を認め,茎状突起症候群が疑われた症例を経験した.この症例に対して,デキサメタゾン2mgと2%メピバカイン1mlを茎状突起周辺に注入したところ,薬物療法に抵抗する顔面痛が軽減した.茎状突起症候群の治療は,その原因となる茎状突起を切除する方法が最も効果的と考えられている.しかし,本症候群の確定診断はむずかしく,手術侵襲や合併症,後遺症の可能性を考慮すると,本症例のように侵害受容性の痛みと思われる場合には,糖質コルチコイドと局所麻酔薬の局所注入法が有効と思われる.

Background : It has been demonstrated that a group of minor tranquilizers, benzodiazepines, are able to relax airway smooth muscles. To determine the underlying mechanisms of this phenomenon, the effects of midazolam on the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and tension in airway smooth muscles were investigated. Methods : Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, both [Ca 2+ ] i and isometric tension developments were simultaneously recorded. Results : When the tracheal strips were exposed to a high external K + -solution (40 mM) or 10 -7 M carbachol containing 1.25 mM Ca 2+ , both [Ca 2+ ] i and tension increased rapidly until they reached a plateau (the steady state). During steady-state contraction induced by K + -depolarization or carbachol, the cumulative application of midazolam (10 -7 ∼ 10 -4 M) caused decreases in both [Ca 2+ ] i and tension, in a concentration-dependent manner. During 40 mM K + -induced depolarization, the stepwise increases in the extracellular Ca 2+ concentration induced the stepwise increases in [Ca 2+ ] i and tension. Midazolam (3 X 10 -5 M) inhibited these increases in [Ca 2+ ] i and tension, but had no effect on the [Ca 2+ ] i -tension relationship. In the presence of 3 X 10 -3 M Nicl 2 (a nonselective cation channel blocker), midazolam (3 X 10 -5 M) did not cause any additional reduction of [Ca 2+ ] i or tension during the contraction induced by carbachol (10 -7 M). In the absence of extracellular Ca 2+ , midazolam (3 X 10 -5 M) had no effect on the transient increases in either [Ca 2+ ] i or the tension induced by carbachol (10 -7 M) or caffeine (20 mM). Pretreatment with both 10 -5 M flumazenil (a specific central antagonist of benzodiazepines) and 10 -5 M PK11195 (a specific peripheral antagonist of benzodiazepines) did not influence the effect of 10 -5 M midazolam on [Ca 2+ ] i or tension during the contractions induced by carbachol. Conclusions : Midazolam directly relaxes airway smooth muscles by decreasing [Ca 2+ ] i ; this can be attributed to the inhibition of the influx of extracellular Ca 2+ . Midazolam has no effect on the release of stored Ca 2+ . In addition, midazolam has no effect on Ca 2+ sensitivity of the contractile apparatus. Finally, benzodiazepine antagonists, flumazenil and PK11195, have no effect on this mechanism of direct action of midazolam on airway smooth muscles.

The influence of two inhalational anesthetics, isoflurane and sevoflurane, on the end-systolic pressure-volume relations (ESPVR) of the left ventricle (LV) in situ was investigated in open-chest dogs anesthetized with α-chloralose. The LV volume was measured by a conductance catheter while the LV pressure was measured by a tipmicromanometer. The end-systolic elastance (Ees) of the LV was calculated as the slope of ESPVR which was elicited when the inferior vena cava was transiently occluded. The dogs were randomly assigned to two groups, receiving either 1.3% and 2.6% isoflurane (n=6) or 2.3% and 4.6% sevoflurane (n=6), which are equivalent to 1 and 2 MAC of isoflurane or sevoflurane, respectively. Both isoflurane and sevoflurane produced dose-dependent decreases in the cardiac output to a similar degree. Isoflurane and sevoflurane caused equivalent decreases in Ees of 23% and 16% at 1 MAC, and 48% and 41% at 2 MAC, respectively. Dobutamine 3 μg·kg−1·min−1 produced a simultaneous restoration of Ees and recovery of the cardiac output at 1 and 2 MAC of both isoflurane and sevoflurane. We thus conclude that the depressant effect of sevoflurane on cardiac contractility is almost identical to that of isoflurane in the dog, and they are both reversed by the use of a low dose of dobutamine.

Employing the isometric tension recording method, we studied the role of endothelium or endothelium-derived relaxing factor (EDRF) in the generation of rhythmic oscillations observed in contractile responses to various receptor agonists in isolated rabbit small mesenteric and epicardial coronary arteries. Norepinephrine (NE, 0.1-10 microM) generated oscillatory contraction in endothelium-intact strips from the mesenteric arteries. Similarly, acetylcholine (ACh, 10 microM), histamine (10 microM) and serotonin (10 microM) generated oscillatory contraction in endothelium-intact strips from the coronary arteries. These agonist-induced oscillations in both arteries were consistently eliminated by either endothelial denudation or EDRF pathway inhibitors including NG-nitro L-arginine (30 and 100 microM), oxyhemoglobin (3 and 10 microM) and methylene blue (3 and 10 microM). In contrast, EDRF releasers such as ACh or A23187 augmented the oscillations in the endothelium-intact strips. SNP (0.03-30 microM) failed to generate oscillations in NE (10 microM)-preconstricted endothelium-denuded strips from the mesenteric arteries. In conclusion, these agonist-induced oscillations are probably mediated through EDRF. The inability of SNP to generate oscillations suggests the obligatory role of the endothelium in generation of the oscillations. The oscillatory release of EDRF by endothelial cells may be responsible for generation of the oscillations.

Our experiences of hyperthermic isolated limb perfusion with administration of carboplatin, interferon-beta or a combination of both are reported. Administration of high doses of these reagents was well tolerated by patients with melanoma without severe complications after the treatment. A total of 8 patients underwent this therapeutic modality. Remarkable clinical improvement was seen in the first patient, who was in Stage III at the time of the perfusion. Histopathological findings indicated severe damage to the melanoma cells after the operation. Prophylactic hyperthermic perfusion was performed in 6 other patients with Stage II-III melanoma of the lower limb. None of them have shown any signs of recurrence 1-10 months later. The activities of natural killer cells or T lymphocytes appeared to be increased when the perfusion was carried out with concomitant administration of both carboplatin and interferon-beta. These results suggest that hyperthermic isolated limb perfusion with carboplatin and/or interferon beta administration is effective in patients with advanced stage melanoma.

The effects of endotoxin on glutathione concentrations in rabbit plasma and liver were investigated. Lipopolysaccharide (2 mg/kg) from Escherichia coli was administered intravenously to seven male Japanese rabbits. In the liver, the concentrations of reduced glutathione (GSH) started to decrease, and those of oxidized glutathione (GSSG) started to increase 1 hr after the endotoxin administration, resulting in a progressive decline in the hepatic GSH/GSSG ratio. In the arterial plasma, the concentrations of both GSH and GSSG started to increase 1 hr after the endotoxin administration. Because the increase in the concentrations of GSSG was greater than that in the concentrations of GSH, the GSH/GSSG ratio in the plasma decreased as did that in the liver. These changes in glutathione concentrations occurred simultaneously with the increase in serum osmolality, but earlier than the decrease in the arterial ketone body ratio, both of which are thought to be useful markers for liver damage. It was concluded that endotoxin induced an increase in the plasma concentrations of GSH as well as GSSG, and that the changes in plasma glutathione status might be useful markers of endotoxin-induced damage in organs, including the liver.

It has been known that carbon tetrachloride-induced liver damage in starved rats is ameliorated simply by restoration of feeding. An analogue of dichloroacetate has been reported to ameliorate carbon tetrachloride-induced liver damage, and dichloroacetate has been shown to have a variety of effects on fuel metabolism. We investigated simultaneously the effects of dichloroacetate on liver damage and on circulating fuels in rats exposed to carbon tetrachloride. The effects of carbon tetrachloride varied with the rat's condition. In starved rats, the liver damage was more severe, and serum ketone body concentration decreased. In non-starved rats, the liver damage was not as severe and the serum ketone body concentration increased. The administration of dichloroacetate ameliorated liver damage both in starved and in non-starved rats given carbon tetrachloride: the administration of dichloroacetate protected from the liver damage particularly in starved rats. There were associated changes in the concentrations of circulating fuels. When the pyruvate-lowering effect of dichloroacetate was diminished in carbon tetrachloride-injected, starved rats, the alanine aminotransferase-lowering effect of dichloroacetate was also diminished. We propose that dichloroacetate's effect on fuel metabolism may produce a hepato-protective effect.

Whole body oxygen consumption was measured using a thermodilution fibreoptic catheter in two patients undergoing extracorporeal hepatic resection. Each patient had virtually normal liver function before the operation. Anaesthesia was induced and maintained in a standard fashion and a venovenous bypass instituted. The anhepatic periods were 302 and 157 min. Upon removal of the liver, the oxygen consumption decreased by about 40% (50 mL/min), while the mixed venous oxygen saturation increased by about 15%. Following re-implantation, the oxygen consumption recovered and increased transiently above control values, while the mixed venous oxygen saturation changed in a reciprocal way. Monitoring whole body oxygen consumption instead of hepatic oxygen consumption seemed helpful in estimating restoration of blood flow and functions in the liver after reperfusion. It was also suggested that changes in oxygen consumption as well as those in cardiac output and haemoglobin concentration could be predicted easily by continuous monitoring of mixed venous oxygen saturation during the peri-anhepatic period.

Despite the wide clinical use of protamine, the precise mechanisms of its hypotensive effects during reversal of heparin anticoagulation have not been elucidated fully. We, therefore, investigated the effects of protamine on isolated human small mesenteric arteries, both in the absence and presence of heparin, employing the isometric tension recording method. Protamine exerted vasodilating actions in the absence of heparin: 1) protamine (> or = 50 or 150 micrograms/mL) inhibited (P < 0.05) both norepinephrine (1 microM)- and high K+ (40 mM)-induced contractions in the presence of extracellular Ca2+ both in endothelium-intact and -denuded tissues; and 2) protamine inhibited (P < 0.05) norepinephrine (1 microM)-induced, but not caffeine (10 mM)-induced, contractions in the absence of extracellular Ca2+. Such vasodilating actions were blocked almost completely in the presence of heparin. We conclude that only protamine, but not a heparin-protamine complex, has a vasodilating action on the human arteries.

Many studies have demonstrated that lidocaine directly relaxes airway smooth muscle. The underlying mechanisms, especially in relation to Ca2+ mobilization, remain to be elucidated.Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, intracellular Ca2+ concentration ([Ca2+]i) and isometric tension were simultaneously measured.In cases of 40 mM K(+)-induced contraction and 1 microM acetylcholine (ACh)-induced contraction, the cumulative application of lidocaine (10(-6) approximately 3 x 10(-3) M) caused a concentration-dependent decrease in [Ca2+]i and tension, and almost complete relaxation. To examine the effect of lidocaine on Ca2+ sensitivity of the contractile apparatus, the [Ca2+]i-tension relationship was determined by changing the extracellular Ca2+ concentration during 40 mM K+ induced depolarization, with and without treatment with lidocaine. Although treatment with 1 mM lidocaine inhibited increases in both [Ca2+]i and tension induced by extracellular Ca2+, it had little effect on the [Ca2+]i-tension relationship. In the presence of 1 microM ACh, the [Ca2+]i-tension relationship shifted markedly to the left, thereby indicating an increase in Ca2+ sensitivity of the contractile apparatus; this shift was inhibited by 1 mM lidocaine. In the absence of extracellular Ca2+, 1 mM lidocaine inhibited the release of stored Ca2+ induced by 1 microM ACh, but not that by 20 mM caffeine.Lidocaine directly relaxes airway smooth muscle by decreasing [Ca2+]i. In addition, lidocaine inhibits the ACh-induced increase of Ca2+ sensitivity of the contractile apparatus, although it has little effect on Ca2+ sensitivity during high K+ depolarization. The decrease in [Ca2+]i is attributed to inhibition of the influx of extracellular Ca2+, as induced by high K+ depolarization and by ACh, and to the inhibition of the ACh-induced release of stored Ca2+.

We studied the changes in end-tidal CO(2) (ET(CO)(2)) and systemic responses after tourniquet deflation in spontaneously breathing and ventilation-controlled patients during orthopedic surgery of both the upper and/or the lower extremities. In most patients, increases in ET(CO)(2), heart rate, and Pa(CO)(2), as well as decreases in blood pressure and pH were observed. In every spontaneously breathing patient, the respiratory rate began to increase before the ET(CO)(2) reached a maximum. Arterial blood gas analysis suggested that the increase in ET(CO)(2) closely reflected the increase in Pa(CO)(2). Our study yielded new information on the ET(CO)(2) changes as follows: 1) the time for ET(CO)(2) level to reach a peak (peak time) was almost constant despite the considerable differences in the increases in ET(CO)(2) both in spontaneous breathing and ventilation-controlled groups and the peak time in the former group was shorter than that in the latter group; and 2) it was suggested that the increase in ET(CO)(2) in the spontaneously breathing patients was smaller than that in ventilation-controlled patients when both patients were subjected to the same conditions on tourniquet time and tourniqueted area. Our data showed that the increase in ET(CO)(2) (or Pa(CO)(2)) can be large and prolonged in some situations. Thus, we recommend continuous ET(CO)(2) monitoring and the proper hyperventilation at tourniquet deflation in order to minimize any adverse effects of acidosis.

sive to conventional therapies. 4 We report a patient with medial temporal lobe epilepsy (MTLE), in whom the administration of propofol failed to diminish intraoperative seizure activity that was confined to the medial temporal lobe on electrocorticography (ECoG). The seizure activity was finally controlled with diazepam. A 12-year-old boy had a 10-year history of intractable complex partial seizure disorder. The seizures began with the aura of an unpleasant epigastric sensation, followed by unresponsiveness and oral automatism for 2 to 3 minutes. The seizures were often secondarily generalized, and remained refractory to the maximal dosage of carbamazepine, phenytoin, and zonisamide. Interictal electroencephalography (EEG) showed frequent paroxysmal activities in the left frontotemporal region. Magnetic resonance imaging demonstrated left hippocampal atrophy with a T2 prolonged area, indicating hippocampal sclerosis. Positron emission tomography with [ 18 F] fluorodeoxy glucose, and single-photon emission computed tomography with technetium- 99 m-ethyl-cysteinate dimer revealed hypometabolism and hypoperfusion, respectively, in the left medial temporal lobe. Thus, the patient was diagnosed with left MTLE. A left anterior temporal lobectomy with hippocampectomy was then scheduled. He received no sedative premedication. Anesthesia was induced with propofol 160 mg and vecuronium bromide 8 mg, and the trachea was intubated. Fentanyl 0.3 mg and droperidol 7.5 mg were administrated during the first 2 hours with 67% nitrous oxide (N2O) in oxygen (O2) also given for maintenance. The patient was mechanically ventilated with end-tidal CO2 at 30 to 35 mmHg.

We recorded spinal cord evoked potentials (SCEPs) and spinal somatosensory evoked potentials (spinal SEPs) in 30 operations following stimulation of the epidural spinal cord and the peripheral nerve, respectively, to compare their feasibility as an intraoperative technique for spinal cord monitoring. SCEPs produced quicker responses and had larger amplitudes with simpler waveforms. SCEPs could reflect residual function of the pathological spinal cord and predict the postoperative clinical outcome, findings which are not observed with spinal SEPs. Moreover, SCEPs had a much higher sensitivity to spinal cord insult. Therefore, we conclude that the SCEPs were more appropriate indicator than the spinal SEPs as an intra-operative monitoring method for spinal cord function.

To understand the strategy of anesthesiologists regarding intra-operative transfusion, we analyzed cases at Kyushu University Hospital. During the last four months, intra-operative blood transfusions were performed in 172 out of 1, 525 (11.3%) surgical operations done in our operating room. Among these 172 cases, as many as 30% (55 cases) were managed by autologous transfusions, either preoperative deposition or intra-operative cell saving. For red cell transfusion, red cell concentrates derived from 400ml of donated blood were used in most cases (224/236, 95%). The critical hematocrit level at which anesthesiologists introduced blood transfusion was 25%, instead of 30%, the generally accepted level. All platelet transfusions were done with platelet concentrates obtained by single donor apheresis. These results indicate that adverse reactions of homologous blood transfusions such as post-transfusion hepatitis or post-transfusion graft-versus-host disease are well understood by anesthesiologists, and efforts to reduce transfused blood units were made. Only 15% of all transfused blood units were of fresh frozen plasma. This means that anesthesiologists recognized that fresh frozen plasma should be used to supplement coagulation factors. However, one of the problems to be settled is the overuse of albumin solutions. In the present series, 5% albumin solutions were administered in over 60% of transfused cases to maintain colloid osmotic pressure, but many cases could have been managed by alternative measures.

先天性第V因子欠乏症を合併する小児の口蓋裂形成術の麻酔管理を経験した.手術に先立ち正常血漿添加試験を行い,活性部分トロンボプラスチン時間(APTT)が第V因子活性の指標として有用であること,血漿添加によりAPTTが短縮されることを確認した.術中の第V因子補充療法として新鮮凍結血漿(FFP)投与を行い,初回補充として20ml/kg投与した.小児患者では循環系に対する容量負荷が懸念されることからFFP投与と同時に脱血を行った.初回投与後にAPTT値が40秒と改善したのを確認後,手術を開始した.術後2日間に10ml/kgのFFP追加投与を2回行いAPTT値を50秒以下に維持し,全経過を通じ異常な出血をみることもなく良好な経過を得た.