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The purpose of this prospective study was to evaluate the effects of one-lung ventilation on the activity of the cardiac autonomic nervous system. Ten adult patients who underwent thoracotomy were endotracheally intubated with a double-lumen tube under general anesthesia using isoflurane. After induction of anesthesia, a continuous, 256-sec electrocardiogram (ECG) was obtained during bilateral lung ventilation (control) followed by recordings during one-lung ventilation of each side. Using the R-R interval tachograms obtained for the 256-sec ECGs, 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 and the HF/LF ratio were analyzed using the fast Fourier transform algorithm. Log(HF), which indicates parasympathetic activity, increased during one-lung ventilation on each side, but did not differ between ventilated sides. Log(LF), which represents sympathetic and parasympathetic activity, increased similarly to log(HF) on both sides. Log(HF/LF), the balance of the sympathetic and parasympathetic activity, did not change during one-lung ventilation. We suggest that one-lung ventilation alone does not substantially affect the cardiac autonomic nervous system.

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.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.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.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.

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.

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 (p0.05), 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) (p0.05), and were decreased by L-NAME in EPA (p0.05), 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.

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.

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.

An abnormally accelerated Ca-induced Ca release (CICR) rate is known to be correlated with malignant hyperthermia susceptibility (MHS).To analyze significant clinical findings concerning CICR rate and develop a computer program for its prediction in human MHS.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.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%.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.

A 31-year-old man with pulmonary alveolar proteinosis underwent whole lung lavage using differential lung ventilation under general anesthesia with propofol and fentanyl. Left lung lavage was performed under the differential lung ventilation using extracorporeal lung assist. A month later, right lung lavage was performed under the differential lung ventilation alone. We compared left lung lavage with right one in the effects on heart rate variability and relationships between heart rate and arterial pressure. In the left lung lavage compared with the right one, arterial pressure was maintained higher; sympathetic nervous activity was kept tonic as shown in the power spectral analysis of heart rate variability; coherency showed lower; and a phase relationship analysis indicated a delay of almost 180 degrees. Therefore, we conclude that left lung lavage affected the cardiac autonomic nervous activity more than right one in differential lung ventilation.

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.

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.

Brain metastasis from hepatocellular carcinoma (HCC) is a rare, yet perplexing problem in patients with cancer. We report on 5 patients with metastasis of HCC to the brain after radical hepatectomy. Intrahepatic recurrence occurred in 3 patients, and distant metastasis to sites other than the brain was observed in 3 patients (lung, 2; bone, 1). The symptoms for brain metastasis included headache, hemiparesis, and vomiting. Hemorrhage was found in 4 of 5 patients. All patients had a single nodular lesion in the brain. The alpha-fetoprotein levels were more than 10,000 ng/ml in 4 patients. Two patients underwent surgical resection, 1 received cranial irradiation, and 2 were administered corticosteroids. The interval between diagnosis of the primary cancer and detection of brain metastasis ranged from 2 to 54 months. The mean survival period was only 3 months after diagnosis of brain metastasis. All 5 patients died of neurologic causes. Because no effective treatment for brain metastasis from HCC is available, further study is needed.

Some genetic studies have shown a linkage between malignant hyperthermia susceptibility (MHS) and chromosome 19q or the skeletal muscle ryanodine receptor (RYR1) gene. Some types of MHS seem to be caused by an abnormality of calcium-induced calcium release (CICR). We analyzed the linkage of RYR1 gene polymorphisms in Japanese MHS families and investigated the correlation between genetic evidence of RYR1 gene mutations and an accelerated rate of CICR. We studied 63 subjects who were referred to our institute for investigation of MHS. CICR rates were measured by the skinned fiber method in 23 subjects. DNA samples were collected from 63 individuals belonging to 22 unrelated families. Restriction fragment length polymorphism (RFLP) analyses on the RYR1 locus and hypervariable microsatellite analysis were performed. We found one family with a linkage between acceleration of the CICR mechanism and a group of RFLPs. In CICR tests, ten of the 11 patients who had presented with fulminant MH showed accelerated rates of CICR. Analysis for the mutation C1840T, which was performed in 63 samples, did not demonstrate an alteration in any of the patients. Although we found heterozygotes in RFLP studies, we did not recognize a specific relationship between the acceleration of CICR and the RFLPs. We suggest a linkage between the acceleration of CICR and an abnormal human RYR1 gene in MHS. These results also suggest that heterogeneity exists for MH. We conclude that genetic tests cannot replace CICR tests or caffeine-halothane contracture tests with muscle biopsy as a diagnosing test for MH in the near future.

In this study we examined whether continuous monitoring of jugular bulb venous oxygen saturation (SjO2) is applicable for the evaluation of cerebral hypoperfusion during carotid endarterectomy (CEA). The subjects were 25 patients who underwent elective CEA under general anaesthesia. After the carotid stump pressure (SP) was measured, SjO2 and the somatosensory evoked potentials (SEP) were monitored during the carotid test clamping for 10 min. There was no alteration in cardiovascular and respiratory status during the test clamping. No correlation was observed between SEP amplitude and SP (r = 0.16, p = 0.25). However, at clamping, SjO2 decreased from 70 to 64% (p0.01) with a reduction in SEP amplitude from 2.0 to 1.6 microV (p0.01). After declamping, SjO2 increased from 65 to 70% (p0.01) with a recovery in SEP from 1.6 to 1.9 microV (p0.01). The changes in SEP amplitude and SjO2 correlated (r = 0.66, p0.001). These results suggest that continuous monitoring of SjO2 is superior to SP measurement in the prediction of cerebral hypoperfusion caused by carotid clamping and applicable to CEA.

In this report, we evaluate the indications of, and present our recent strategy for, cavernous hemangioma of the liver. Seven patients with cavernous hemangiomas of the liver, who underwent hepatic resection were enrolled in this study. The lesions were located in the right lobe in 3 patients, the left lobe in 2, and in both the right and left lobes in 2. The longest diameter of the lesions ranged from 1.4 to 14.5 cm (mean, 8.2 cm). The indications for hepatic resection were symptomatic lesions in 3 patients, lesions suspected to be hepatocellular carcinoma in 2, and symptomatic and growing lesions during follow-up in 2. Right lobectomy was performed in 2 patients, left lobectomy with caudate lobectomy in 1 patient, and minor hepatic resection in the other 4 patients. One of the patients who underwent minor hepatic resection had recently received laparoscopy-assisted hepatic resection and one of the three patients who received transfusion during surgery was given an autotransfusion. There were no mortality, and morbidity was minimal. In conclusion, hepatic resection, including laparoscopy-assisted procedures, was considered a safe treatment. Hepatic resection for cavernous hemangioma should be performed only in patients with moderate to severe symptoms, complicated lesions or both, because most benign lesions have a good natural course. Furthermore, in the future, less invasive surgical procedures should be used whenever possible to treat these benign liver tumors.

BACKGROUND-MATERIALS: Dopamine is known to induce hyperglycemia in both animals and man, but the precise mechanism by which this occurs has not yet been fully clarified. We investigated whether dopamine has any direct effect on glucose release from hepatocytes through the glycogenolytic and/or gluconeogenic pathways, and at the same time determined the main type of adrenergic receptor involved in glucose release, using primary cultured rat hepatocytes. METHODS-RESULTS-CONCLUSIONS: Glycogen-rich and glycogen-depleted hepatocytes were prepared in order to study glycogenolytic and gluconeogenic glucose release, respectively. After exchanging the culture medium for Hanks-HEPES buffer containing no glucose (but with fructose for the glycogen-depleted hepatocytes), dopamine was added to these two groups of hepatocytes at final concentrations of 0, 10(-7), 10(-6), 10(-5), and 10(-4) M. The amount of glucose released from the hepatocytes 30 minutes after adding dopamine at concentrations of 10(-5) and 10(-4) M were significantly higher than those obtained at dopamine concentrations of 0, 10(-7) and 10(-6) M. Tne increase in glucose release at the dopamine concentration of 10(-5) M was inhibited by 10(-5) M propranolol, but not by 10(-5) M phentolamine. Our findings suggest that dopamine has a direct effect on hepatocytes, increasing glucose release via both the glycogenolytic and gluconeogenic pathways and mediated by beta-adrenergic receptors.

Thoracoscopic microwave coagulation therapy (MCT) is a new therapeutic approach for hepatocellular carcinoma (HCC) in segments VII and VIII, which allows minimal access to the tumor and complete tumor ablation. In this study, four patients with HCC in segments VII and VIII underwent thoracoscopic MCT as a less invasive therapeutic option due to advanced liver cirrhosis and/or severe complications. Tumor sizes ranged from 15 to 30 mm in diameter and the tumors were well differentiated in 2 patients, moderately in one and poorly in one patient. Microwave irradiation was performed at an 80 W output with a 60-sec duration via a thoracoscopic route and the total duration ranged from 4 to 24 min (mean: 17 min). Patients recovered rapidly to preoperative conditions and no mortality was occurred. Complications were observed in one patient, including pleural effusion and fever elevation, but were cured conservatively. Postoperative computed tomography (CT) showed complete tumor ablation with a cancer-free margin, which is thought to be equivalent to a limited hepatic resection. This preliminary study suggests that thoracoscopic MCT might be a new, less invasive option providing a cure for HCC in segments VII and VIII in patients with advanced liver cirrhosis and severe complications.

We evaluated the efficacy of and the indications for palliative reduction surgery as a procedure to improve the prognosis of hepatocellular carcinoma (HCC) patients with multiple intrahepatic metastases. From January 1986 to October 1997, 25 HCC patients with multiple intrahepatic metastases who underwent necessary palliative reduction surgery due to advanced disease, were participated in the study. The 1-, 3-, 5-year survival rates of 25 patients with reduction surgery were 54.7%, 29.9%, 22.4%, respectively. Moreover, the 1-, 3-, 5-year survival rates of patients with some postoperative supplemental treatment were 68.8%, 41.2% and 30.9%, respectively. All 6 patients who had been alive for more than 3 years had had primary tumors with diametric sizes of approximately 5 cm and had undergone, at most, one segmentectomy. These patients received postoperative supplemental treatments. The indication for palliative reduction surgery for HCC patients with multiple intrahepatic metastases was patients with a relatively small primary tumor (around 5 cm) which could be removed by one segmentectomy or less.

BACKGROUND-MATERIALS: Much extracellular fluid administration is required during major surgery because of the functional loss of extracellular fluid. In the present study we investigated the effect of manipulation of the intestines and mesentery in a rat laparotomy model. METHODS-RESULTS-CONCLUSIONS: The results showed that manipulation significantly increased the amount of protein exudated into the peritoneal space and induced a marked histopathological inflammatory response including polymorphonuclear leukocyte infiltration and mast cell degradation. These findings suggest that the inflammatory response induced by manipulation may, at least in part, explain the underlying mechanism of 'third space' loss during abdominal intestinal surgery.

A case of successful endotracheal intubation using an image intensifier in a 9-year-old boy with tracheal stenosis was reported. After the induction of anesthesia, the trachea was observed by use of mobile surgical X-ray apparatus under artificial ventilation using a face mask. Because the tracheal wall of the stenotic part was smooth and seemed soft, we selected a plain 5.5 mm diameter endotracheal tube and intubated under observation using an image intensifier. We observed the tube pass through the stenotic part of the trachea without difficulty. We consider that endotracheal intubation under image guidance is useful in a patient with tracheal stenosis.

Buckling of the transesophageal echocardiography probe was encountered in 6 of 23 patients (26.1%), although no complication occurred. When buckling occurred, acquisition of images and manipulation of the probe became difficult, resistance was felt when withdrawal of the probe was attempted, and the probe was fixed in the extreme ante- or dorsiflexion. In this situation, the probe was carefully advanced into the stomach, in which the buckled probe was unfolded, and then withdrawn to the esophagus. Buckling of the probe tip is not uncommon at insertion of the probe, especially when using a flaccid probe in an anesthetized patient. A TEE operator should be aware of the possibility of buckling. Unusual resistance associated with buldging of the submandibular region is a sign of a folded-up probe tip. Use of laryngoscopy is recommended in order to avoid inserting the buckled probe into the esophagus.

Four patients underwent surgical removal of pheochromocytoma under balanced anesthesia with fentanyl, sevoflurane and epidural anesthesia combined with continuous infusion of nicardipine and nitroglycerin. Circulation was stable during the operation in all the patients. There were no serious hypertension and hypotension, arrhythmia and pulmonary edema during the postoperative period. We conclude that the anesthetic management of patients with pheochromocytoma for adrenalectomy using balanced anesthesia with continuous infusion of nicardipine and nitroglycerin is one of the most useful anesthetic methods.

A patient with Budd-Chiari syndrome who underwent a new surgical technique; venoplasty of right hepatic vein and liver portion of inferior vena cava using veno-venous bypass, was reported. The patient was 31 year-old man whose weight and height were 55 kg and 157 cm, respectively. During the anesthetic management of this patient, we encountered following problems; continuous massive bleeding, profound hypothermia and hemodynamic derangement. These problems were similar to those of liver surgery using veno-venous bypass such as extracorporeal liver surgery and liver transplantation.

The effect of vitamin E on halothane-induced liver damage was studied in guinea pig halothane hepatitis. Twenty animals were divided into 3 groups, consisting of a control group, a halothane group and a vitamin E + halothane (H) group. The animals in the control group (n = 6) were allowed to inhale air only. The animals in the halothane group (n = 6) and the vitamin E + H group (n = 8) were allowed to inhale 1% halothane with air. Animals in the vitamin E + H group were additionally injected with 30 mg kg-1 of vitamin E 30 minutes prior to inhalation of halothane. Blood was aspirated from the heart immediately after sacrificing to measure the serum activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). A microsomal suspension was prepared from the excised liver. Then the amount of thiobarbituric acid (TBA) reactive products in the microsomes were measured. The amount of tissue TBA-reactive products was increased by inhalation of halothane. The increase in the amount of TBA-reactive product was inhibited by the administration of vitamin E. The serum GPT activity was increased by halothane inhalation. Increased serum GOT and GPT activity were inhibited by the administration of vitamin E. These results demonstrated that vitamin E suppressed halothane-induced liver damage in the guinea pig by inhibiting lipid peroxidation.

Three patients with abnormal hemostasis during surgery were reported. They were monitored by thrombelastography (TEG). The first case was a 48 year old male who underwent extravivo hepatectomy. TEG showed hypo-coagulability during anhepatic phase. After reperfusion to the liver, the coagulability determined by TEG returned to a normal pattern. The second patient was a 32 year old female who underwent laparotomy to stop bleeding for cervico-vaginal laceration after delivery. The patient had been in severe hemorrhagic shock, and massive blood transfusion and fluid administration were performed. TEG showed remarkable hypocoagulability probably due to blood dilution and consumption coagulopathy. When TEG returned to a normal pattern after administration of fresh frozen plasma and fresh whole blood, the abnormal bleeding stopped. The third patient was a 48 year old male who underwent resection of metastatic brain tumor. He had hepatocellular carcinoma and liver cirrhosis. During surgery, abnormal bleeding was seen at surgical field, when TEG revealed remarkable hyper-fibrinolysis. After antifibrinolytic therapy coupled with replacement therapy, TEG returned to a normal pattern and the abnormal bleeding ceased. We conclude that TEG is a useful bed side monitor for the diagnosis of coagulopathy and hyper-fibrinolysis during surgery.

We analyzed anesthetic records to obtain formulae to evaluate circulatory stability during anesthesia. Eight anesthesiologists graded circulatory stability based on 67 consecutive anesthetic records. Median of the grade, on the maximum of 10 points, was determined as the criterion variables for multiple regression analysis. The explanatory variables were: age, weight, height, heart rate, anesthesia time and systolic as well as diastolic blood pressure. Interdependent parameters were not used for this analysis. Adequate numbers of the explanatory variables were determined when Akaike's information criterion (AIC) was minimal. Two different analytical methods were used. One of the most suitable formulae to express circulatory stability throughout anesthesia was: 9.28-0.012 x A-0.017 x SPmax + 0.013 x SPmin-0.009 x HRmax A: age (year) SPmax: maximal value in systolic blood pressure (mmHg) SPmin: minimal value in systolic blood pressure (mmHg) HRmax: maximal value in heart rate (bpm) We conclude that these formulae obtained are useful to evaluate circulatory stability during anesthesia.

The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation.

The effects of various volatile anesthetics on intramuscular Ca(2+)-related functions were studied with the skinned fiber technique in guinea pig skeletal muscles. All the volatile anesthetics tested significantly enhanced Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) at clinical concentrations with negligible effects both on Ca2+ sensitivity of the contractile system and on Ca2+ uptake by the SR. A comparison was made of the enhancing effect of several volatile anesthetics on CICR at clinical concentrations. Halothane was the most potent, followed by methoxyflurane, isoflurane, enflurane, sevoflurane and diethyl ether. If CICR plays an important role in triggering MH, this order of volatile anesthetics on their enhancing effect on CICR, also corresponds to their potency in triggering MH.

The effects of in vivo pretreatment with phenobarbital (PB), thiopental (TP), thiamylal (TA), pentobarbital (PT), and secobarbital (SB) on hepatic microsomal enzymes, and the effects on anaerobic halothane dehalogenation, aminopyrine N-demethylation, and aniline hydroxylation in the microsomes were studied in male Wistar rats. Three hundred twenty mumol/kg (0.1 ml) of PB, TP, TA, PT, SB, or 0.1ml of 0.9% saline were administered daily, intramuscularly, for periods of one day up to ten days. Daily administration of PB, TP, TA, or PT induced cytochrome P-450, NADPH-cytochrome P-450 reductase and/or cytochrome b5. However, administration of SB did not induce these enzymes. The potency of these enzyme inductions ranged in descending order as follows: PB, TP, TA, and PT. After five days of daily administration of PB, TP, or TA, the production of the anaerobic halothane metabolite, CDFE, increased to 187%, 134%, and 130% of the control, respectively. The production of another halothane metabolite, CTFE, likewise increased to 197%, 168%, and 163%. However, pretreatment with PT or SB had no effect on anaerobic halothane dehalogenation. Aminopyrine N-demethylation also increased after five days of daily administration of PB, TP, and TA. However, aniline hydroxylation decreased after five days of daily administration of TA. Other barbiturates had no effect on aniline hydroxylation. In this study we showed that whereas PT and SB did not enhance anaerobic halothane dehalogenation, PB, TP and TA did. We conclude that not only PB, and also TP and TA, may be enhancing factors in halothane hepatotoxicity. We recommend that, if barbiturates are necessary, SB and PT be used in the preadministration of halothane anesthesia.

The effect of hemorrhage and retransfusion on the rhythmic contraction of mesenteric lymphatic vessels was studied in 24 rats, anesthetized with pentobarbital. The rats were divided into four groups according to the amount of blood withdrawn: 0.5ml/100g body weight (BW), 1ml/100g, 2ml/100g, and 2.5ml/100g. Immediately following hemorrhage at the rate of 0.5ml/100g/min, lymphatic contraction frequencies were decreased to 67 +/- 12.5, 45 +/- 24.7, 43 +/- 33.1, and 31 +/- 17.8% of the prehemorrhage values in each of the above four groups, respectively (p less than 0.01). Twenty minutes after hemorrhage, lymphatic contraction frequencies were decreased to 70 +/- 17.2, 46 +/- 36.8, and 34 +/- 41.3% in the 0.5ml/100g, 2ml/100g, and 2.5ml/100g, respectively (p less than 0.05). Immediately following hemorrhage, the lymphatic contracted diameters were also reduced to 77 +/- 9.7 and 61 +/- 9.0% of the prehemorrhage values in the 1ml/100g and 2.5ml/100g groups, respectively (p less than 0.01). Twenty minutes after hemorrhage, all withdrawn blood was reinfused. Lymphatic contraction frequency and contracted diameter recovered after retransfusion in each group but 20 minutes after retransfusion, the lymphatic contraction frequency in the 2ml/100g group was still decreased to 42 +/- 30.3% (p less than 0.01). Lymphatic contraction frequency not only decreased proportionately with hypotension during hemorrhage but after retransfusion contraction frequency correlated directly with the mean arterial pressure 20 min after hemorrhage. These data suggest that mean arterial pressure and by inference capillary blood flow and tissue oxygenation are major factors regulating lymphatic vasomotion.

Pentane, which is an index of lipid peroxidation, was formed in a mixture of microsomes, carbon tetrachloride (CCl4) and NADPH. Trichloromethyl radical adduct of the N-tert-butyl-alpha-phenylnitrone-trichroromethyl (BPN) was also formed in the mixture with BPN. The formation of pentane and the radical adduct were reduced in the presence of paraquat. Furthermore a spectrophotometric study showed that substrate-induced difference spectra in the Soret region (Type I) caused by CCl4 and microsomes were changed after adding paraquat. We conclude that paraquat inhibits the lipid peroxidation mediated by the radical intermediate of CCl4 by inhibiting the mixed function oxidase system.

Pentane was measured in a mixture of guinea pig liver microsomes and carbontetrachloride (CCl4) in the presence of nicotineamide adenine dinucleotide phosphate (NADPH) and under anaerobic conditions by gas chromatography. Pentane of 0.2 pmol/mg protein/min was formed in the presence of NADPH without CCl4. Pentane formation increased to 2.0 pmol/mg protein/min in the presence of CCl4 and NADPH. This reaction required an anaerobic atmosphere, 2.1 mmol/litter of NADPH and 13.4 mmol/litter of CCl4 under optimal conditions. The formation was reduced in the presence of oxygen, glutathione, vitamin E and metyrapone. These results clearly show that pentane is formed by lipid peroxidation initiated by the free radical cleavage products of CCl4, which are anaerobically produced by NADPH-dependent microsomal enzymes. We conclude that pentane is a good index of in vitro lipid peroxidation via microsomal NADPH-P-450 enzyme systems.

In 22 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB), we studied the influence of CPB on the level of lipid peroxides (LPO) in plasma by means of measuring the time course of plasma LPO level during and after CPB. We expressed LPO level, which was measured by thiobarbituric acid reaction, as the level of malondialdehyde. In our preliminary study, it was found necessary to correct the plasma LPO level diluted by priming fluids of CPB machine and the concentration of plasma protein was fitted for its correction. In the following study, we used the plasma LPO level corrected by the concentration of plasma protein. LPO were significantly decreased since the initiation of CPB (1.669 +/- 0.208 versus pre-CPB 1.785 +/- 0.158 log nmol MDA/gm protein, p less than 0.05) to the post CPB 30 minutes, except around 60 minutes after initiation of CPB (1.735 +/- 0.242 log nmol MDA/gm protein, p greater than 0.05). As the initial change (the values at 30 minutes after CPB initiation) may express the effect of CPB directly in this time course of LPO, we analyzed the initial change on different background factors. By ordinary analysis of the initial change, as to the effect of type of disease (congenital and acquired), LPO were decreased in the acquired group (1.617 +/- 0.197 versus pre-CPB 1.779 +/- 0.163 log nmol MDA/gm protein, p less than 0.05). At that time the acquired group was significantly different from the congenital group (1.799 +/- 0.191 versus pre-CPB 1.800 +/- 0.157 log nmol MDA/gm protein, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of halothane on the electrical activity of inspiratory neurons of the nucleus tractus solitarius (NTS) was studied in decerebrate, paralyzed, mechanically ventilated cats. Simultaneous recording of the activity of the neurons of the NTS and the phrenic nerve was done to identify the inspiratory neurons. Cells whose firing activity was synchronous with that of the phrenic nerve were considered inspiratory neurons. Administration of 1% and 1.5% halothane in oxygen induced a dose-dependent depression of the cell activity (spikes/s) with the cervical vagi intact or severed. Five and ten minutes after inhalation of 1% halothane, the cell activity (mean +/- SE) expressed as per cent of the control was 55.3 +/- 9 and 27 +/- 7, respectively (P less than 0.001), before bilateral cervical vagotomy. The corresponding values for 1.5% halothane were 25 +/- 10.1 and 5.6 +/- 3, respectively. Upon termination of halothane administration, the cell activity gradually returned toward the control level. The cell response to halothane was not affected by bilateral cervical vagotomy. Hypercapnia produced by inhalation of 5% CO2 increased the cell activity, but halothane caused profound depression of the cells even in the presence of hypercapnia. Based on these results, it may be concluded that: halothane has inhibitory effects on the activity of the inspiratory neurons of the NTS; and halothane-induced respiratory depression has a central component and that the NTS may serve as a site of action of halothane for its respiratory depressant effect.

The purpose of this study was to examine the effects of alfentanil applied to the surface of the spinal cord and the effects of intravenously administered alfentanil on noxiously evoked activity of dorsal horn neurons. Extracellular single neuron recordings were obtained from wide dynamic range neurons in 26 decerebrate cats with transected spinal cords. Spinally administered alfentanil, 25 micrograms or 50 micrograms, caused 36 and 86% suppression of noxiously evoked activity, respectively. Maximum mean suppression was achieved at 24 and 21 min after 25 micrograms, and 50 micrograms, respectively. Intravenous naloxone, 0.1 mg, when tested, completely reversed the suppression. Spontaneous recovery to control values occurred within 2 hr. Intravenously administered alfentanil, 12.5 micrograms/kg or 25 micrograms/kg, produced suppression of 43 and 89%, respectively, with maximum mean suppression observed at the 6- and 3-min time points, respectively. Complete recovery after intravenous administration was seen within 30 min. This study, using a sensitive neurophysiologic assay, demonstrates the important differences in onset and duration of drug effects that must be considered when comparing the responses of spinal cord neurons to intravenously administered narcotics and narcotics applied directly to the surface of the spinal cord.

Microsomal fractions were prepared from the liver of rabbits to investigate the effects of paraquat (methyl viologen) on generation of metabolites of halothane under the optimal aerobic and anaerobic conditions. Halothane (CF3CHClBr) is known to undergo oxidative and reductive biotransformation in the hepatic mixed function oxidase system including cytochrome-P450 reductase and cytochrome P450. The results showed that paraquat inhibited generation of metabolites of halothane under these conditions. Generation of the aerobic metabolite, trifluoroacetic acid (CF3COOH), and anaerobic metabolites, 2-chloro-1, 1, 1-trifluoroethane (CF3CH2Cl) and 2-chloro-1, 1-difluoroethylene (CF2CHCl), were inhibited 50% by 4.96 mM and 35.3 mM paraquat, respectively. Possible mechanisms were speculated on to account for the inhibitory effects: one being the impaired formation of halothane-cytochrome P450 complex by addition of paraquat, and the other the diversion of electrons from cytochrome-P-450 reductase to generate active paraquat radicals. It is concluded that paraquat inhibits NADPH-dependent biotransformation of halothane catalyzed in mixed function oxidase system.

The optimal composition of eluant for trifluoroacetic acid (TFAA) analysis by ion-exchange chromatography was determined and a preliminary study to detect TFAA, a metabolite of isoflurane, in bile of rabbits during and after inhalation of isoflurane was made. The optimal composition of eluant for TFAA analysis by ion-exchange chromatography was determined to be a solution of 2mM Na2CO3 and 4mM NaHCO3. Rabbits were divided into 4 groups; A group: 1 hr inhalation of 2% isoflurane, B group: 2 hr inhalation of 2% isoflurane, C group: 2 hr inhalation of 3% isoflurane, and D group: 2 hr inhalation of 4% isoflurane. The maximum biliary TFAA concentration in groups A, B, C and D averaged 17.5 +/- 1.4 microM (mean +/- S.D.) at 105 min, 37.1 +/- 11.5 microM at 315 min, 54.5 +/- 9.4 microM at 585 min and 34.4 +/- 12.1 microM at 555 min after termination of inhalation. Cumulative excreted amounts of biliary TFAA for 20 hours were 746 nmols in A group (8 hours), 3,421 nmols in B group, 6,582 nmols in C group and 3,267 nmols in D group. Half-lives of biliary excreted TFAA were 63 min, 325 min, 478 min and 546 min, respectively. These results showed that ion-exchange chromatography is more convenient for detecting TFAA as a metabolite of isoflurane than isotachophoresis, gas chromatography, paper chromatography and thin layer chromatography and that TFAA was determined as a biliary metabolite of isoflurane in the rabbit.

In this study, background factors were determined in 108 surgical patients who showed depression in phagocytic and bacteriocidal activity with nitroblue tetrazolium reduction test. Control subjects consisted of 4 healthy males and 4 healthy females whose age ranged from 25 to 38 years. The background factors associated with the depressed neutrophil phagocytic and bacteriocidal activity in surgical patients were renal insufficiency, liver cirrhosis, hypoproteinemia, diabetes mellitus, long-term administration of steroids and immunosuppressants, obesity, anemia, aging and malignant tumors. These depression factors closely resembled those generally considered to be involved in increased susceptibility to infections.