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Publications and source records attributed to Shigeru Saito.
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PURPOSE: It is common clinical practice to use dopamine to manage the reduction in blood pressure accompanying epidural blockade. As propofol is a high-clearance drug, propofol concentrations can be influenced by cardiac output (CO). The purpose of the present study was to investigate the effects of dopamine infusions on propofol concentrations administered by a target-controlled infusion system during epidural block under general anesthesia. METHODS: 12 patients undergoing abdominal surgery were enrolled in this study. Anesthesia was induced with propofol and vecuronium 0.1 mg.kg(-1), and maintained using 67% nitrous oxide, sevoflurane in oxygen and constant infusion of propofol. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 6.0 microg.mL(-1) at intubation and 2.0 microg.mL(-1) after intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from the epidural catheter and dopamine infusion at 5 microg.kg(-1).min(-1), CO and effective liver blood flow (LBF) were measured using indocyanine green. Blood propofol concentration was also determined using high-performance liquid chromatography. RESULTS: At one hour after epidural block and dopamine infusion, CO was significantly increased from 4.30 +/- 1.07 L.min(-1) to 5.82 +/- 0.98 L.min(-1) (P < 0.0001), and effective LBF was increased 0.75 +/- 0.17 L.min(-1) to 0.96 +/- 0.18 L.min(-1) (P < 0.0001). Propofol concentration was significantly decreased from 2.13 +/- 0.24 microg.mL(-1) to 1.59 +/- 0.29 microg.mL(-1) (P < 0.0001). CONCLUSIONS: Propofol concentrations decrease with an increase in CO, suggesting the possibility of inadequate anesthetic depth following catecholamine infusion during propofol anesthesia.
PURPOSE: Systemic ketamine suppresses several types of chronic pain. Although ketamine is used as a general anesthetic agent, the analgesic effect of systemic ketamine for early-stage postoperative pain is not clear. We investigated the efficacy and mechanism of systemic ketamine in a rat model of postoperative pain. METHODS: An incision was made in the plantar aspect of the left hind paw in male Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey filaments. The anti-hypersensitivity effect of systemic or intrathecal administration of ketamine was determined every hour after making the incision. We examined the effects of intrathecal pretreatment with yohimbine, an alpha2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine. We also examined the effect of systemic ketamine on the c-fos immunoreactivity in the spinal cord. RESULTS: Systemic administration of ketamine at doses from 3 to 30 mg.kg(-1) produced anti-hypersensitivity effects in a dose-dependent manner. Intrathecal administration of ketamine had no effect. There was no significant difference between effects of pre- and post-incisional administration. Intrathecal pretreatment with yohimbine (10 microg) or methysergide (15 microg) completely reversed the anti-hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos expression in laminae I-II in the dorsal horn of the lumbar spinal cord ipsilateral to the paw incision. CONCLUSIONS: The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.
PURPOSE: Several ss-adrenergic-blocking drugs have been used during electroconvulsive therapy (ECT) to stabilize the hemodynamic alterations following electrical stimulation. The effects of two ultra-short acting ss-adrenergic-blocking drugs, esmolol and landiolol, on systemic and cerebral circulation were studied during ECT. METHODS: In the first study (n = 15), dose-dependent hemodynamic changes were studied when landiolol was administered immediately after induction of anesthesia. In the second study (n = 12), effects of esmolol and landiolol on systemic and cerebral circulation were compared. Patients in Study 1 received three doses of landiolol, and patients in Study 2 received two types of ss-adrenergic-blocking drugs, in a randomized cross-over design in a series of ECT trials. RESULTS: In the first study, 0.25 to 0.5 mg.kg(-1) landiolol induced a lower heart rate after the electrical stimulation compared to vehicle (P < 0.01). Landiolol did not have significant effects on blood pressure. In the second study, heart rate was stabilized by 1.0 mg.kg(-1) esmolol iv or 0.5 mg.kg(-1) landiolol iv. Increase in mean blood pressure was ameliorated by esmolol (P < 0.01), but not by landiolol. Mean cerebral blood flow velocity in the middle cerebral artery increased at one to two minutes after the electrical stimulation regardless of the use of ss-adrenergic-blocking drugs (P < 0.01). Muscular and electroencephalographic seizure durations were not significantly altered by the ss-adrenergic-blocking drugs. CONCLUSION: Landiolol suppresses heart rate elevation during ECT without affecting blood pressure. Cerebral blood flow velocity in the middle cerebral artery is not affected by the use of either esmolol or landiolol.
The present study investigated plasma propofol concentration for optimal sedation and total body clearance in patients who required sedation for mechanical ventilation after esophagectomy. Seven patients after esophagectomy were enrolled in this study. Plasma propofol concentrations were measured with high performance liquid chromatography. Total body clearance was calculated from the steady-state concentration. The infusion rate of propofol for achieving the sedation score of level 3 (drowsy, responds to verbal stimulation) was 1.74 +/- 0.82 mg kg(-1) h(-1) (mean +/- SD, n = 7) when the plasma propofol concentration and the total body clearance were 0.85 +/- 0.24 microg ml(-1) and 1.83 +/- 0.54 l min(-1) (mean +/- SD, n =7), respectively.
Recent guidelines have stated that anesthesia for electroconvulsive therapy (ECT) should be administered by a specially trained anesthesiologist, and that anesthesiologists have overall responsibility, not only for anesthesia itself, but also for cardiopulmonary management and emergency care. Accordingly, anesthesiologists who administer anesthesia for ECT should have sufficient knowledge regarding the physiologically and pharmacologically unique effects of ECT. Electrical current during ECT stimulates the autonomic nervous system and provokes unique hemodynamic changes in systemic and cerebral circulation. Excessive alterations in heart rate, blood pressure, and cardiac functions should be prevented by medications with anticholinergic and antihypertensive agents. Ventilation should be adequately maintained to ensure the efficacy of the therapy and to stabilize the hemodynamics immediately after the electrical stimulation. Reports of serious complications of this therapy are not frequent; however, patients with ischemic heart disease or cerebrovascular problems must be managed with special care to prevent myocardial infarction or neurological disorders. Safe physical management by anesthesiologists greatly contributes to the establishment of ECT under muscle relaxation. To maintain social confidence and to refine the therapy, anesthesiologists should play an essential role both in clinical activities and in laboratory research.
X-ray fluoroscopy-guided percutaneous radiofrequency facet rhizotomy is used to treat chronic low back pain. The traditional fluoroscopic approach to the medial branch of the posterior rami, however, is associated with a small incidence of complications. We describe a new method for radiofrequency lumbar facet rhizotomy in which computed tomography (CT) fluoroscopy is used to guide needle placement. Three patients with chronic intractable low back pain underwent CT fluoroscopy-guided percutaneous facet rhizotomy. After the safest and shortest route to the target site was determined on the CT image, the needle was advanced along the predetermined route under real-time CT fluoroscopy. When the needle tip was located at the target site, electrical stimulation was applied to verify proper electrode placement. After confirming the clinical effect and lack of complications under test block with a local anesthetic, denervation was performed using radiofrequency current. Pain scores of all patients were reduced after the procedure without any complications such as paralysis or neuritic pain. None of the patients complained of severe discomfort during the procedure. CT fluoroscopy-guided percutaneous lumbar facet rhizotomy appears to be safe, fast, and effective for patients with lumbar facet pain.
Gasserian ganglion block is an established treatment for trigeminal neuralgia. A landmark approach assisted by X-ray fluoroscopy is the most common method; however, visualization of the foramen ovale is difficult in some cases. Here we report two cases in which a novel technique using modern computed tomography (CT) fluoroscopy was employed. A 63-year-old woman suffering pain in the maxillary nerve area was treated by thermogangliolysis under CT fluoroscopy. The patient was positioned on a CT stage with the head in an overhanging position. The CT gantry was set at an oblique angle to obtain a coronal view of the foramen ovale. The safest and shortest route to the foramen was designed using the CT image and a 22-gauge insulated needle was advanced following the designed route under CT fluoroscopy. The effect of the nerve block was estimated by injection of a test dose of mepivacaine, after which the ganglion was thermally coagulated at 90 degrees C. Satisfactory analgesia was obtained in this case without any complications. Another patient (65 years old) was also treated by the same technique, and satisfactory pain relief was obtained. In conclusion, CT fluoroscopy-guided Gasserian ganglion thermolysis is considered a safe, quick, and effective treatment for trigeminal neuralgia.
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BACKGROUND: Heavy metal ions can cause allergic and inflammatory reactions that might be associated with in-stent restenosis. This randomized multicenter clinical study was designed to determine if carbon ion-implanted stents reduce luminal late loss by blocking heavy metal ion diffusion into the surrounding tissue. METHODS: A total of 225 patients with 230 native coronary lesions were randomly assigned to receive either a carbon ion-implanted Arthos Inert stent (group 1, n = 113) or a bare metal Arthos stent (group 2, n = 117). The primary endpoint was in-stent luminal late loss at 6-month angiographic follow-up, and the secondary endpoints were the 6-month angiographic restenosis rate and the occurrence of the major adverse cardiac events (MACE) including death, nonfatal myocardial infarction, and target lesion revascularization at 12 months. RESULTS: The baseline characteristics were similar in the 2 groups. In-hospital events did not occur in any patients. Angiographic follow-up at 6 months was obtained in 184 lesions (80%). At follow-up, the luminal late loss was similar in the 2 groups (0.91 +/- 0.77 mm in group 1 vs 0.88 +/- 0.80 mm in group 2, P = .79), and the angiographic restenosis rates were 11.0% in group 1 and 16.1% in group 2 (P = .31). The occurrence rates of MACE at 12 months were 9.1% in group 1 and 10.4% in group 2 (P = .73). CONCLUSIONS: The initial and long-term outcomes of the carbon ion-implanted stent were excellent. However, it did not improve long-term outcomes vs the bare metal stent.
Autonomic nervous systems have important roles for survival of victims under hypobaric hypoxic condition. In the present study, we assessed the correlation between arterial oxygen saturation (Sp O 2 ) and heart rate variability (HRV) to identify the autonomic nervous responsiveness among trekkers at high altitude (n = 21). HRV was analyzed by the maximum entropy method. Sp O 2 among subjects at 3456 m (495 mm Hg) was 80% +/- 5% (mean +/- SD; range, 69%-93%). Sp O 2 and percentile entropy, and Sp O 2 and low-frequency variability, had positive correlation ( r = 0.455 and 0.518, respectively). Sp O 2 value among subjects with mountain sickness symptoms was not different from that among subjects without the symptoms. In conclusion, autonomic responses among high-altitude trekkers may be blunted under hypobaric hypoxic conditions. Deterioration of autonomic function measured by HRV might be more sensitive to hypoxia than clinical symptoms at high altitudes.
OBJECTIVE: Toll-like receptors (TLRs) recognize microbial ligands and host products that are released during tissue damage, the so-called "danger signals." This study was conducted to determine whether changes in TLR-4 and TLR-2 expressions can be detected in the trophoblasts at the placental bed of women with and without preeclampsia. STUDY DESIGN: Placental bed biopsy specimens were obtained from women with: (1) normal term pregnancies with and without labor (each n = 20); (2) preeclampsia who delivered preterm (n = 15); and (3) preterm labor and intact membranes with and without chorioamnionitis (each n = 15). The expression pattern of TLR-4 and TLR-2 in the trophoblasts was analyzed by double immunohistochemistry. RESULTS: (1) The median percentage of TLR-4 positive interstitial trophoblasts was significantly higher in patients with preeclampsia than in patients with preterm labor without or with histologic chorioamnionitis (P = .0002 and P = .02, respectively). (2) The median percentage of TLR-2 positive interstitial trophoblasts was not different among the study groups (P>.05). (3) TLR-4 positive trophoblasts were also frequently immunoreactive to activated nuclear factor-kappaB, tumor necrosis factor-alpha, and M30 (a specific apoptosis antigen for trophoblast). (4) Lipopolysaccharide treatment inhibited the migration of trophoblast cell lines in vitro. CONCLUSION: TLR-4 protein expression is increased in interstitial trophoblasts of patients with preeclampsia. We propose that "danger signals" at the feto-maternal interface, which are recognized by trophoblasts through TLR-4, may play a key role in the creation of a local abnormal cytokine milieu. This suggests a novel mechanism that links the activation of the innate immune system through TLR-4 and preeclampsia.
Acyclovir and less frequently, vidarabine are (or have been) used in the treatment of varicella-zoster virus (VZV) infection and are administered either intravenously (vidarabine) or orally (acyclovir, up to five times per day). The pharmacological bases of the administration interval were modeled in vitro in this study. Incubation of VZV-infected cultures with acyclovir or vidarabine for 24, 48, 72 and 96h showed similar duration-dependent anti-viral activities as assessed by a plaque-reduction assay. Treatment with vidarabine for only 8h/day for 4 days (intermittent treatment) showed anti-VZV activity equivalent to that of continuous treatment for 4 days in terms of the inhibitory dose that reduced plaque formation by 50% (IC(50)). In contrast, intermittent treatment with acyclovir exhibited a 7.9 times higher IC(50) value than that of continuous treatment. The mode of inhibition of expression of most of viral protein was similar in both drugs, but the degree of inhibition was different for each protein. Thus, vidarabine with a limited period of treatment showed anti-VZV activity comparable to continuous treatment with acyclovir, indicating the longer duration of anti-viral activity of vidarabine.
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STUDY OBJECTIVE: To examine the age-related difference between elderly and young patients in the effect of propofol on cerebrovascular carbon dioxide (CO(2)) reactivity. DESIGN: Prospective controlled study. SETTING: University hospital. PATIENTS: Elderly (older than 70 years, n = 13) and young patients (younger than 25 years, n = 13) scheduled for elective orthopedic surgery. INTERVENTIONS: After induction of anesthesia, a 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window, from which mean blood flow velocity of the middle cerebral artery was measured continuously. MEASUREMENTS: After obtaining baseline values of velocity of the middle cerebral artery, arterial blood gases, and cardiovascular hemodynamics, end-tidal CO(2) was decreased by increasing the ventilatory frequency by 2 to 5 breaths per minute. Measurements were repeated when end-tidal CO(2) decreased and remained stable for 5 to 10 minutes. Cerebrovascular CO(2) reactivity, at propofol doses of 5 and 10 mg/kg/h, was measured. MAIN RESULTS: No significant differences were observed between the 2 groups in baseline absolute and relative CO(2) reactivity. However, there were significant differences between the 2 groups in absolute or relative CO(2) reactivity at a propofol dosage of 5 mg/kg/h. (Absolute CO(2) reactivity in young patients: 2.1 +/- 0.8 cm/s/mm Hg; elderly: 1.6 +/- 0.4* cm/s/mm Hg. Relative CO(2) reactivity in young patients: 7.4% +/- 1.6%/mm Hg; in the elderly: 6.5% +/- 0.9%*/mm Hg; unpaired t test, *P < .05). In contrast, there were no significant differences between the 2 groups in terms of absolute or relative CO(2) reactivity at a propofol dosage of 10 mg/kg/h. CONCLUSIONS: Cerebrovascular CO(2) reactivity in elderly patients was lower than that in young patients at a propofol dosage of 5 mg/kg/h.
STUDY OBJECTIVE: The goal of this study was to characterize the hemodynamic response to propofol vs propofol with fentanyl when used for sedation after esophagectomy or cardiac surgery. DESIGN: Prospective, randomized, controlled study. SETTING: University Hospital, Intensive Care Unit. PATIENTS: Thirty patients undergoing elective cardiac surgery and 26 patients undergoing esophagectomy were examined. INTERVENTION: Patients were randomized to receive propofol (0.5 mg/kg bolus over 10 minutes, followed by continuous infusion at 1 mg/kg per hour) with or without fentanyl (2.0 microg/kg per hour) to achieve sedation overnight while in the intensive care unit. Randomization was performed in a double-blind manner. MEASUREMENT: Mean arterial pressure (MAP) was monitored throughout the treatment period, and sedation level was measured. Sedation level was targeted to achieve a Ramsay score of 4. MAIN RESULTS: The number of patients experiencing a greater than 20% drop in baseline MAP was higher in cardiac patients receiving propofol alone (11 of 15 patients, 73%) than in cardiac patients receiving propofol with fentanyl (4 of 15 patients, 27%). Furthermore, the time of optimal sedation was lower in the cardiac patients who received propofol than in cardiac patients who received propofol with fentanyl group (propofol alone, 79%; propofol with fentanyl, 88%). In contrast, there was no difference in the number of esophagectomy patients experiencing a greater than 20% drop in baseline MAP or in the mean time of optimal sedation when comparing the 2 treatment regimens. CONCLUSIONS: Propofol has a differential effect on hemodynamics and sedation when comparing patients after cardiac surgery and esophagectomy.
In both rodent and human systems, there is an emerging consensus that immunoregulatory activity specific for donor alloantigens is enriched in the CD4(+)CD25+ T cell population. The absence of CD4(+)CD25+ regulatory T (Treg) cells induces severe immunodeficiency with autoimmune disease, dermatitis and fatal infections in humans and mice. CD4(+)CD25+ Treg cells play a critical role in peripheral tolerance, transplantation tolerance and maternal tolerance to the fetus. Although both human and mouse CD4(+)CD25+ Treg have potent regulatory properties, surface phenotypes of human CD4(+)CD25+ Treg cells are not exactly the same as those of mouse CD4(+)CD25+ Treg cells. Murine CD4(+)CD25+ T cells are homogenous and exhibit regulatory function. On the other hand, CD4(+)CD25high T cells are the only cells which exhibit regulatory function in humans. Humans CD4(+)CD25low cells have no ability for immunosuppression. CD4(+)CD25high T cells inhibit the immunostimulation of conventional T cells through cell-to-cell contact or immunosuppressive cytokines such as interleukin 10 and transforming growth factor-beta. As another mechanism of immunosuppression, CTLA-4 on CD4(+)CD25+ regulatory T cells up-regulate indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells which play important roles for immunosuppression. Here, we review the differences between humans and mouse Treg cells and the role of CD4(+)CD25+Treg during pregnancy.