Analysis of human cultured myotubes responses mediated by ryanodine receptor 1.

Malignant hyperthermia is a life-threatening condition caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Identifying patients predisposed to malignant hyperthermia is done through the Ca-induced Ca release test in Japan. We examined the intracellular calcium concentration in human cultured muscle cells and compared the sensitivity of myotubes to ryanodine receptor type 1 activators based on the Ca-induced Ca release rate. We assessed the utility of this method as an identifying test for predisposition to malignant hyperthermia. Muscle specimens were obtained from 34 individuals undergoing the Ca-induced Ca release test. We cultured myotubes from residual material and monitored changes in intracellular calcium concentration after exposure to the ryanodine receptor type 1 activators caffeine, halothane and 4-chloro-m-cresol by measuring fura-2 fluorescence. We determined the half maximal effective concentrations (EC50) for the test compounds in each myotube and calculated cut-off points using receiver operating characteristic curves. Seventeen patients each were classified into the accelerated and non-accelerated groups based on their Ca-induced Ca release rate. The EC50 values for caffeine, halothane and 4-chloro-m-cresol of the accelerated group were significant lower than those of the non-accelerated group (P < 0.001, P < 0.001 and P < 0.001, respectively). The calculated cut-off points of EC50 values for caffeine, halothane and 4-CmC were 3.62 mM, 2.28 mM and 197 microM, respectively. An increased sensitivity to ryanodine receptor type 1 activators was seen in myotubes in the accelerated group. This functional test on human cultured myotubes indicates that the alteration of their intracellular Ca2+ homeostasis may identify the predisposition to malignant hyperthermia.

Effects of propofol on calcium homeostasis in human skeletal muscle.

Malignant hyperthermia is a pharmacogenetic skeletal muscle disorder of intracellular calcium (Ca2+) homeostasis with an autosomal dominant inheritance. The objective of this study was to investigate the safety of propofol by investigating its effects on calcium homeostasis and its effect sites in human skeletal muscles. Muscle specimens were obtained from 10 individuals with predisposition to malignant hyperthermia. In skinned fibre experiments, we measured the effects of propofol on the Ca(2+)-induced Ca2+ release and the uptake of Ca2+ into the sarcoplasmic reticulum. Ca2+ imaging in primary myotubes was employed to analyse propofol-mediated alternations in the Ca2+ regulation and propofol-induced Ca2+ responses in the presence of Ca2+ channel blocker or Ca(2+)-induced Ca2+ release inhibitor. Increased Ca2+ release from the sarcoplasmic reticulum and inhibition of Ca2+ uptake into the sarcoplasmic reticulum were not observed with 100 microM propofol. A rise of Ca2+ was not seen under 100 microM propofol and the EC50 value for propofol was 274.7 +/- 33.9 microM, which is higher than the clinical levels for anaesthesia. Propofol-induced Ca2+ responses were remarkably attenuated in the presence of Ca2+ channel blocker or Ca(2+)-induced Ca+ release inhibitor compared with the results obtained with caffeine. We conclude firstly that propofol is safe for individuals with predisposition to malignant hyperthermia when it is used within the recommended clinical dosage range, and secondly that its mode of action upon ryanodine receptors is likely to be different from that of caffeine.

A comparison of the effects of prolonged (>10 hour) low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane anaesthesia on hepatorenal function in orthopaedic patients.

This study compared the effects of low-flow sevoflurane, high-flow sevoflurane and low-flow isoflurane on hepatorenal function during and after more than 10 hours of anaesthesia. Twenty-five patients scheduled for elective orthopaedic surgery were categorized into three groups; low-flow sevoflurane (fresh gas flow at 1 litre/min, n = 9), high-flow sevoflurane (5 l/rmin, n = 7), or low-flow isoflurane (1 l/min, n=9). Inspiratory compoundA concentrations were measured. The groups had similar duration of anaesthesia and exposure to anaesthetic agents. The area under the curve of concentration (mean, SD) of compound A in the low-flow sevoflurane group (359.8, 106.1 ppm.h) was greater than that in the high-flow sevoflurane group (61.1, 29.3 ppm.h; P<0.01). All groups showed normal plasma creatinine and creatinine clearance, and transient postoperative increases in plasma alanine aminotransferase and alpha glutathione-S-transferase, as well as urinary glucose and alpha glutathione-S-transferase, with no significant differences between groups. There were no significant relationships between the area under the curve of concentration of compound A and the biomarkers. These findings suggest that prolonged anaesthesia with low-flow sevoflurane has similar effects on hepatorenal function to prolonged anaesthesia with high-flow sevoflurane and low-flow isoflurane.

Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of platelets under synergic interaction with endothelial cells.

BACKGROUND: The inhibitory effect of prostaglandin E1 (PGE1) on platelet aggregation is considered an important characteristic of this agent. However, the concentration of PGE1 to inhibit aggregation in vitro is higher than those of clinical use (1 ng/ml). To clarify whether PGE1 at clinically relevant concentrations inhibits aggregation under synergic action with endothelial cell-derived factors (nitric oxide and prostacyclin), we evaluated the minimum effective concentration of PGE1 to enhance the anti-aggregating activity of endothelial cells. METHODS: Inhibitory effects of PGE1 and/or the incubation buffer from cultured porcine aortic endothelial (PAE) cells on human platelet aggregation induced by 2 micro g/ml collagen were examined by turbidimetry. RESULTS: PGE1 concentration-dependently (>3 ng/ml) inhibited aggregation: the incubation buffer from PAE cells stimulated by bradykinin also inhibited aggregation. Bradykinin concentration-dependently increased the anti-aggregating activity of the PAE incubation buffer. The half-maximum effective concentration of bradykinin to inhibit aggregation (95.4+/-22.3 nM) was significantly decreased to 10.3+/-2.5 nM by 0.1 ng/ml PGE1 and to 0.9+/-0.5 nM by 1 ng/ml PGE1, respectively. These indicated that PGE1 (=0.1 ng/ml) inhibits aggregation through synergism with endothelial cells. The synergic effect of PGE1 and the anti-aggregating activity of the PAE cells preincubated with 10 micro M indomethacin for 30 min was more potent than that of these cells preincubated with 1 mM NG-nitro-L-arginine methyl ester. This suggested that the interaction of PGE1 with endothelial cell-derived nitric oxide is more powerful than that with endothelial cell-derived prostacyclin. CONCLUSION: Prostaglandin E1 (=0.1 ng/ml) inhibited platelet aggregation under synergic interaction with endothelial cells.

Heart rate to arterial pressure impulse response during one lung ventilation.

BACKGROUND: Although one lung ventilation (OLV) is commonly used, little is known about the modulation of the autonomic nervous system with OLV while under general anesthesia. As the frequency domain and time domain analyses are powerful analytic tools, we investigated their modulation during OLV. METHODS: Patients undergoing thoracic surgery were classified into two groups: those who did (group A, n=8) and those who did not (group N, n=8) receive atropine. After a double lumen tube was placed endotracheally, mechanical ventilation of both lungs (BLV) was established at 18 min(-1) while under isoflurane anesthesia. Electrocardiogram, systolic arterial pressure (SAP), and inspiratory flow (Finsp) were digitally recorded as follows: awake before anesthesia; BLV after anesthesia; BLV after intravenous 10 microg kg(-1) of atropine (group A) or not (group N); left OLV; and right OLV. Power spectral analyses of heart rate (HR) and SAP were computed by determining low-(LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.40 Hz) components, and impulse response analysis was executed among HR, SAP, and Finsp. Impulse responses were assessed by the maximum values in the time domain. RESULTS: In frequency domain analysis, atropine depressed LF and LF/HF but not HF in HR variability, while no difference was observed between right OLV and left OLV. The heart rate to SAP impulse response was maintained at a significantly higher level in group A than in group N (905+/-360 vs. 425+/-375 mmHg beats(-1)min(-1)) at right OLV. A significant difference was also observed between left and right OLV within group N. CONCLUSION: Impulse response analysis demonstrated that there is a greater effect on autonomic nervous system modulation during right OLV than in left OLV, which mainly results from a parasympathetic neural linkage origin.

Endoscopic thoracic sympathicotomy in Japan.

We sent our members questionnaire asking about their activities. From December 1992 to the end of 2000, endoscopic thoracic sympathicotomy (ETS) was utilized in 7,017 cases in 50 hospitals and institutes. Of which 6,776 (96.6%) were performed on hypersweating. There have been no deaths related to ETS either during the hospital stay or following discharge. Intraoperative bleeding was reported in 28 cases (0.3%) and an open chest procedure to stop bleeding was required in 6 cases (0.08%). Short term Horner's syndrome after the operation was found in a few cases, however, permanent symptoms were recognized in only 18 (0.28%). The most common postoperative complaint was compensatory sweating on the chest, back, or abdomen. Most of these patients countered this condition by using several methods of prevention or protection and continued on their daily life with little restriction. However, 83 cases (1.2%) experienced severe compensatory sweating and consulted their doctors repeatedly for more than one year. All operators who perform ETS recognized the excellent results for hand and facial sweating. Further, many doctors prefer this procedure as a first treatment for vascular disorders in upper extremities.

Propofol relaxes extrapulmonary artery but not intrapulmonary artery through nitric oxide pathway.

The object of this study was to compare vasorelaxing responses to propofol by the intrapulmonary artery (IPA) and the extrapulmonary artery (EPA), and to identify the mechanisms of action. Rat pulmonary arterial rings were isolated and suspended in organ chambers where isometric tension development was measured under optimal resting tension. All pulmonary arterial rings were pre-contracted with phenylephrine. Propofol (Diprivan) and the vehicle (10% Intralipid) were administered cumulatively in the presence or absence of N(omega)-nitro-L-arginine methyl ester (L-NAME). Sodium nitroprusside (SNP), a nitric oxide donor, was administered cumulatively. Propofol relaxed both EPA and IPA in a dose dependent manner (p<0.05), while the vehicle alone showed no effect. The vasorelaxing responses to propofol were significantly higher in EPA than IPA at higher concentrations (10(-4) M and 10(-4.5) M) (p<0.05), and were decreased by L-NAME in EPA (p<0.05), though it had no effect in IPA. The concentration for SNP causing 50% relaxation was not significantly different between the two arteries. We concluded that the response of smooth muscle to nitric oxide was the same between EPA and IPA; however, the vasorelaxing mechanisms of propofol seemed to be different between them at higher doses, suggesting that a mechanism exists and operates through the nitric oxide pathway.

[Patient-controlled epidural analgesia with bupivacaine and fentanyl suppresses postoperative delirium following hepatectomy].

Postoperative delirium occurs frequently following major surgery, especially after hepatectomy. We hypothesized that better methods of postoperative pain control would decrease postoperative delirium. To clarify the magnitude of postoperative pain and incidence of postoperative delirium in hepatectomy patients, subjects received patient-controlled epidural analgesia (PCEA) using bupivacaine and fentanyl (Group P), or continuous epidural mepivacaine (Group E) following intraoperative epidural administration of morphine. The magnitude of postoperative pain was estimated by use of an analgesic adjuvant and delirium was classified as mild (insomnia, disturbance of sleepwake cycle), moderate (disorientation, hallucination), or severe (restlessness, confusion, agitation), based on the medical records. Analgesic adjuvant usage was less in Group P than in Group E, while the incidences of moderate and severe delirium were significantly less frequent in Group P than in Group E (35.7% versus 75.0%, and 14.3% versus 50.0% respectively). Moreover, less amount of antipsychotic drugs was given in Group P than in Group E. These results suggest that the better pain relief and patient satisfaction provided by PCEA contributed to a decrease in the incidence of delirium, because of continuous opioid administration and patient-control analgesia. We concluded that PCEA with bupivacaine and fentanyl can limit postoperative delirium following hepatectomy.

Small dose of prostaglandin E(1) increases cardiac output without altering blood volume.

STUDY OBJECTIVE: To investigate the effect of small dose of intravenous (IV) prostaglandin E(1) (PGE(1)) on blood volume (BV) and cardiac output (CO) by pulse dye-densitometry (PDD) in patients administered isoflurane anesthesia. DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: 14 ASA physical status I and II adult patients undergoing elective neurosurgery. INTERVENTIONS: Patients were randomly assigned to either the PGE(1) group (n = 7) or the control group (n = 7). Anesthesia was induced with thiamylal, fentanyl, and vecuronium, and maintained with isoflurane and nitrous oxide. When the cardiovascular system stabilized after craniotomy and incision of the dura mater, we administered a small dose of PGE(1) at a rate of 0.02 microg/kg/min (PGE(1) group) or saline at a rate of 2 mL/min (control group). MEASUREMENTS AND MAIN RESULTS: Blood volume, CO, and mean transit time (MTT) were measured by PDD before and 60 minutes after the start of administration. At the same timing, mean arterial pressure (MAP), heart rate (HR), and central venous pressure (CVP) were measured, and systemic vascular resistance (SVR), cardiac index (CI), and CO/BV were computed. As for MAP, there was no significant difference within a group and between groups. In the PGE(1) group, significant increases were noted in CI from 2.54 +/- 0.46 to 3.24 +/- 0.83 (mean +/- SD) L/min/m(2) (p < 0.05), in CO/BV from 0.90 +/- 0.24 to 1.19 +/- 0.33 (p < 0.05), and in HR from 65.7 +/- 10.1 to 74.9 +/- 12.1 bpm (p < 0.05), and a significant decrease was observed in MTT from 22.3 +/- 6.5 to 18.2 +/- 5.1 seconds (p < 0.05 ). Cardiac index and CO/BV in the PGE(1) group increased higher than in the control group, while BV, CVP and SVR remained consistent in both groups. CONCLUSIONS: A small dose of PGE(1), low enough not to provoke hypotension, increased CO without alterations in BV. The increase in CO seemed to be mainly due to an increase in HR.

A prospective multicenter trial to determine the incidence of transient neurologic symptoms after spinal anesthesia with phenylephrine added to 0.5% tetracaine.

The addition of vasoconstrictors for spinal anesthesia is controversial, since an increase in the incidence of transient neurologic symptoms (TNS) has been reported. A multicenter, randomized, double-blind study was conducted to assess the effectiveness of spinal anesthesia with phenylephrine in addition to tetracaine as well as the incidence of neurological complications. We studied 64 patients with comparable demographic characteristics who were scheduled for elective surgery for a lower limb, or a gynecological or urological procedure. The patients were allocated randomly into 2 groups. Group P (n = 34) received 0.5% tetracaine in 10% glucose with 0.025% phenylephrine, while group C (n = 30) received 0.5% tetracaine in 10% glucose. Our results showed that only 2 patients (6.7%) in group C experienced TNS, and their symptoms disappeared within 72 hr after anesthesia, while none of the patients (0%) in group P complained of symptoms. The incidence of TNS was thus not significantly different between the two groups. Six hours after the sensory block, group P patients demonstrated sensory disturbance, with the median spinal dermatome corresponding to the L1 segment. Moreover, systolic blood pressure in group P was significantly higher than that in group C, 5 min, 15 min, and 20 min after injection. The incidence of TNS in the present study does not seem to be greater after surgery with spinal anesthesia using 0.5% hyperbaric tetracaine and 0.5 mg phenylephrine than without phenylephrine. Randomized, double-blind, cross-over trials with a larger sample size would be required in the future to obtain more reliable results.

Prediction of accelerated Ca-induced Ca release rate by clinical findings in malignant hyperthermia susceptible subjects.

BACKGROUND: An abnormally accelerated Ca-induced Ca release (CICR) rate is known to be correlated with malignant hyperthermia susceptibility (MHS). OBJECTIVE: To analyze significant clinical findings concerning CICR rate and develop a computer program for its prediction in human MHS. PATIENTS AND METHOD: Using data from 146 subjects who had received a muscle biopsy for the determination of CICR rate, because of their anesthesia-related MHS history, we analyzed 23 different clinical features. There were 71 subjects with an abnormally accelerated CICR rate and 75 with a normal rate. Accelerated CICR rate was used as the objective variable whilst clinical findings and ages were used as independent variables and control variables, respectively. A multiple logistic regression model was employed for the analyses and the most suitable formulae for prediction were determined for use in the development of a computer program. RESULTS: The following 8 clinical findings were determined to be the most significant: the presence of muscle rigidity, the most serious PaCO2 reading (mmHg), peak body temperature (degree C), body temperature rate of increase over 15 minutes (degree C/15 minutes), most serious arterial pH reading, administration of dantrolene, improvement of acidosis with dantrolene, and time elapsed to peak body temperature after administration of anesthetics (minutes). By ranking the subject ages into 14 groups, we were able to minimize the prediction error rate with each corresponding formula. The computer program developed for prediction whilst consisted of these formulae yielded a sensitivity of 80% and a specificity of 86%. CONCLUSION: This method of prediction may contribute to the accurate prediction of CICR rate at the bedside. For clinical convenience, we will distribute the computer program upon request.

Glucose loading during primary culture has opposite effects on the viability of hepatocytes exposed to potassium cyanide and to iodoacetic acid.

Whether or not to apply nutritional pretreatment and how to do so are controversial issues with respect to the liver about to undergo aggressive intervention. We studied the effects of glucose loading on the viability of hepatocytes that were subsequently exposed to the inhibitors of carbohydrate metabolism, potassium cyanide (KCN) and iodoacetic acid (IAA). After rat hepatocytes were cultured for 24 hours in Leibovitz's L-15 medium containing 0, 10, 20, and 30 mmol/L glucose, the medium was replaced with modified Hanks-HEPES buffer with or without 2.5 mmol/L KCN or 0.5 mmol/L IAA. Lactate dehydrogenase (LDH) activity, lactate concentration, and pH of the supernatant were measured after 0, 2, 4, and 6 hours of exposure to KCN and after 0, 20, 40, and 60 minutes of exposure to IAA. Glycogen and adenosine triphosphate (ATP) contents in the hepatocytes were measured simultaneously. Hepatocytes cultured with various concentrations of glucose for 24 hours stored levels of glycogen in proportion to the glucose concentration in the culture medium without any significant difference in viability. The hepatocytes cultured with higher glucose concentrations maintained a higher ATP content and released less LDH and more lactate, and the pH decreased in the supernatant during exposure to KCN. Conversely, hepatocytes cultured with lower glucose concentrations maintained a higher ATP content and released less LDH during exposure to IAA. In conclusion, prior glucose loading appears to be beneficial for hepatocytes if oxidative phosphorylation is to be inhibited, whereas withholding glucose appears to be beneficial if glycolysis is to be inhibited.

[A comparison of finger and nose probes in pulse dye-densitometry measurements of cardiac output, blood volume and mean transit time].

We compared finger and nose probes in measurement of cardiac output (CO), blood volume (BV) and mean transit time (MTT) with pulse dye-densitometry. These probes were intraoperatively applied to 6 patients under general and continuous epidural anesthesia. Indocyanine green (ICG) 20 mg, was given via peripheral venous route, and CO, BV and MTT were measured with DDG-2001 (NihonKoden, Japan). Eighteen measurements were done successfully. There was no significant difference between F-CO (CO with a finger probe, 4.48 +/- 1.40 l.min-1, mean +/- SD) and N-CO (CO with a nose probe, 4.14 +/- 1.87 l.min-1). F-MTT (32.9 +/- 11.1 sec) was significantly longer than N-MTT (19.9 +/- 6.4 sec, P < 0.01). The limits of agreement of F-CO and N-CO (mean difference +/- 2 SD) were -3.6 and +4.2 l.min-1, respectively. There was a significant negative correlation between differences in MTT and F-CO/N-CO (R2 = 0.448, P < 0.01). There was no significant difference between F-BV (3.97 +/- 1.23 l) and N-BV (3.97 +/- 0.98 l). The limits of agreement of F-BV and N-BV were -1.3 and +1.3 l, respectively. In conclusion, the measured values in BV showed good agreement and reliability with both finger and nose probes, while CO was less reliable when differences in MTT increased.

A formula based on body length for determining the size of an uncuffed endotracheal tube for pediatric cardiac anesthesia.

Three hundred and thirty-four pediatric patients less than 4 years old who underwent surgery for congenital heart disease were retrospectively studied to devise a practical formula for predicting the appropriate size for an uncuffed endotracheal tube for pediatric cardiac anesthesia. Furthermore, this formula was compared with that for non-cardiac anesthesia obtained from 409 patients without congenital heart disease. A simple regression equation between tube size and body length resulted in the simple predictive formula: "tube size = 0.04 x body length + 1.6" for pediatric cardiac anesthesia. This formula had the same slope and an approximately 0.3 mm larger intercept on the Y-axis compared with that for pediatric non-cardiac anesthesia. Therefore, a one-size larger endotracheal tube is more suitable for use in pediatric cardiac anesthesia than in pediatric non-cardiac anesthesia for the same body length.

Perioperative temporal profile of cognitive function in elderly patients undergoing hip surgery.

To test the hypothesis that elderly patients who have surgery for femoral neck fractures may have delirium not only after surgery but before surgery, we prospectively investigated the perioperative temporal profile of cognitive function in such patients. We performed the Abbreviated Mental Test (AMT) six times in each patient (on the day of admission, 3 days after admission, on the day before surgery, 2 days after surgery, 7 days after surgery, and on the day of discharge). Patients were given no premedication and were anesthetized with spinal anesthesia using 0.2% hypobaric tetracaine. Of the 68 patients who were admitted because of a diagnosis of fractured neck of the femur and were scheduled to have surgery, 27 patients were subjected to analysis. Four and three patients showed a significant decrease (3 or more points) in AMT score 2 and 7 days after surgery, respectively. We conclude that surgery may have a stronger impact on cognitive function than environmental change shortly after admission in elderly patients with femoral neck fractures.

[Risk of bradycardia after endoscopic electrocautery of the upper thoracic sympathetic ganglia].

We evaluated risk of bradycardia after endoscopic electrocautery of the upper thoracic sympathetic ganglia (ETS). Enrolled in this study were 24 patients. Bradycardia, defined as heart rate below 50 beats per min continuing for more than 5 min, was found in 12 patients (50%). All patients were divided into two groups; bradycardia group and non-bradycardia group. Age, sex, region of electrocautery, fentanyl dosage, and operation time were not different between the two groups. Power spectral analysis of heart rate variability revealed that sympathetic activity decreased after ETS. Multivariate analysis indicates that postoperative-minimal heart rate depends upon preoperative heart rate at rest. We conclude that careful monitoring after ETS is necessary in a patient with heart rate below 60 bpm preoperatively.

[Pain management for patients with cancer--current problems in a pain clinic].

One hundred and twenty-three patients with early or advanced cancer who had been referred to our pain clinic were studied retrospectively to investigate current problems with pain management for cancer patients. Pain due to advanced cancer and prolonged post-thoracotomy pain were two major reasons for referral. It was found that 51.7% of the patients with advanced cancer had not been treated appropriately with the WHO protocol for cancer pain relief before referral; however, increased administration of morphine did not necessarily relieve cancer pain, and in fact decreased the QOL of some patients; and 47.7% of patients with cancer pain were effectively treated with nerve block therapy. The present investigation also indicates that many patients who had undergone thoracotomy suffered prolonged post thoracotomy pain. Although post-thoracotomy pain was refractory to NSAIDs, trigger point injections with or without intercostal nerve block were effective in 65.4% of such patients. We conclude that further propagation of the WHO protocol for cancer pain relief, appropriate use of nerve block and establishment of practical guidelines for multidisciplinary management of pain are mandatory for improving the QOL of patients with cancer.

Myofascial pain in patients with postthoracotomy pain syndrome.

OBJECTIVE: Postthoracotomy pain syndrome is generally considered to be neuropathic pain due to intercostal nerve injury. However, nonneuropathic pain can also occur following thoracic surgery. We present a series of cases with postthoracotomy pain syndrome in which myofascial pain was thought to be a causative component of postthoracotomy pain syndrome. CASE REPORT: Twenty-seven patients (17 men and 10 women) were treated with trigger point injections, intercostal nerve blocks, and/or epidural blocks. Clinical criteria were used to diagnose the myofascial pain. A visual analogue scale was used, and sensory disturbances were recorded before and after treatment. A trigger point in a taut muscular band within the scapular region, which we diagnosed as myofascial pain, was observed in 67% of the patients. The existence of this trigger point significantly increased the rate of success for the treatments. CONCLUSIONS: Postthoracotomy pain may result, at least in part, from a nonneuropathic origin (myofascial pain). It is recommended that each patient be examined in detail to determine whether there is a trigger point in a taut muscular band within the scapular region. If found, this point is suggested as a good area for anesthetic injection.

Effects of pneumoperitoneum on cardiac autonomic nervous activity evaluated by heart rate variability analysis during sevoflurane, isoflurane, or propofol anesthesia.

BACKGROUND: The effects of pneumoperitoneum on the activity of the cardiac autonomic nervous system have not been completely understood. METHODS: In this study, 45 unpremedicated adult patients who underwent laparoscopic cholecystectomy were anesthetized with either 3.5% sevoflurane, 2% isoflurane, or 8 mg/kg/h propofol (15 patients in each group). The status of cardiac autonomic nervous activity was evaluated by heart rate variability analysis three times: once when the patient was awake, once after induction of general anesthesia, and once after insufflation for pneumoperitoneum. Intra-abdominal pressure was maintained automatically at 10 mm Hg by a carbon dioxide (CO(2)) insufflator. For each measurement, electrocardiogram was recorded for 256 s and played back offline to detect R-R intervals. Power spectral analysis of heart rate variability was applied, and the low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0. 40 Hz) bands of the spectral density of the heart rate variability were obtained from a power spectra of R-R intervals using the fast-Fourier transform algorithm. The HF/LF ratio also was analyzed. RESULTS: Measurements of heart rate variability in the three groups showed similar change. Although the power of HF, which represents parasympathetic nervous activity, did not change, the power of LF, which represents both sympathetic and parasympathetic nervous activity, decreased during the anesthetized stage and increased during the insufflated stage. The HF/LF ratio, which represents the balance of parasympathetic and sympathetic activity, increased after induction of general anesthesia, and decreased after insufflation. CONCLUSIONS: Our results suggest that pneumoperitoneum increases sympathetic cardiac activity. The choice of general anesthetic did not seem to have a major influence on the change in the cardiac autonomic nervous system after induction of pneumoperitoneum for laparoscopic cholecystectomy.

Albumin permeability across endothelial cell monolayer exposed to reactive oxygen intermediates: involvement of reversible functional alteration of the cell membrane Ca2+ channels.

This study was designed to test the idea that the redox state of sulfhydryl (SH)-groups in cell-membrane Ca2+ channels plays a pivotal role in Ca2+ influx, which in turn causes an increase in albumin permeability across the cultured monolayer of porcine pulmonary artery endothelial (PPAE) cells exposed to xanthine/xanthine oxidase (X/XO). Albumin permeability as well as the concentration of intracellular Ca2+ ([Ca2+]i) was increased by X/XO. A H2O2 scavenger (catalase), an iron chelator (o-phenanthroline), and a hydroxyl radical scavenger (dimethyl sulfoxide) inhibited these changes provoked by X/XO, in which intracellular iron-catalyzed hydroxyl radical generation was suggested to be involved. The increase in albumin permeability and [Ca2+]i continued once the PPAE cells were exposed to X/XO. The [Ca2+]i was decreased by a Ca2+ channel blocker, Ni2+, while the removal of Ni2+ increased [Ca2+]i again, suggesting the sustained Ca2+ influx through cell-membrane Ca2+ channels was responsible for the [Ca2+]i elevation. Ni2+ failed to inhibit albumin permeability sustained after the removal of X/XO. In contrast, SH-reducing agents (dithiothreitol and glutathione) inhibited the sustained permeability as well as Ca2+ influx. We concluded that the redox alteration of SH-groups in cell-membrane Ca2+ channels was involved in the increase in albumin permeability after exposure of the endothelial cells to oxidative stress.