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ABSTRACT: We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 03/2013; · 1.08 Impact Factor
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ABSTRACT: We conducted the prospective randomized controlled trial to test that continuous femoral nerve block (CFNB) improves attainment of 120° knee flexion compared to continuous epidural analgesia (CEA). Sixty-six patients scheduled for unilateral total knee arthroplasty were randomized into two groups; infusion of ropivacaine 0.15% into CEA or CFNB to third postoperative days. We studied the time required to attain 120° knee flexion, variations in thigh and calf circumferences around the treated knee, pain scores, rehabilitation milestones, the need for adjuvant analgesics, and side effects. CFNB patients attained earlier knee flexion to 120°, lower variations in thigh and calf circumferences, less pain during rehabilitation, and less need for adjuvant analgesics. CFNB is a better pain management strategy that accelerates knee flexion rehabilitation.
The Journal of arthroplasty 02/2013; · 1.79 Impact Factor
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ABSTRACT: OBJECTIVES:: The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. DESIGN:: Prospective, randomized, animal study. SETTING:: University animal research laboratory. SUBJECTS:: Twenty-eight New Zealand white rabbits. INTERVENTIONS:: Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5-7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. MEASUREMENTS AND RESULTS:: In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. CONCLUSIONS:: In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.
Critical care medicine 12/2012; · 6.37 Impact Factor
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ABSTRACT: Spinal cord injury can have debilitating consequences, commonly resulting in motor dysfunction below the lesion site and the development of chronic pain syndromes. The serotonin pathway is important for inhibiting noxious stimuli and facilitating motor function after spinal cord injury. The serotonin 2C receptor (5HTR2C) has several characteristic features, and is regulated by the amount of serotonin 2C receptor as well as RNA editing and alternative splicing. In this study, we used a rat model of spinal contusion injury to investigate the relationship between the pain threshold and 5HTR2C alternative splicing. The pain threshold was assessed using mechanical stimulation with von Frey filaments. We then used real-time PCR to examine the RNA levels of 5HTR2C in three sections of the spinal cord: the rostral, injury-core, and caudal positions. On postoperative day 12, the pain threshold in injured rats was significantly reduced compared with sham-operated and naïve rats. The total 5HTR2C levels were significantly lower in injured rats than in naïve rats at all positions, and significantly lower in injured rats compared with sham-operated rats at injury-core and caudal positions. The ratio of exon Vb-skipped nonfunctional 5HTR2C mRNA to total 5HTR2C was significantly higher in injured rats compared with naïve rats at the injury-core and caudal positions, and significantly higher in injured rats compared with sham-operated rats at the caudal position. These results indicate that spinal contusion injury, which causes neuropathic pain, induces serotonergic dysfunction. This dysfunction appears to be mediated by decreased 5HTR2C mRNA expression, and alternative splicing. These results confirm the importance of considering splice variants when examining 5HTR2C.
Neuroscience Letters 11/2012; · 2.11 Impact Factor
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ABSTRACT: We previously reported that electroencephalographic (EEG) bicoherence, the degree of phase coupling among the frequency components of a signal, showed 2 peaks during isoflurane anesthesia. Hayashi et al. (Br J Anaesth 2007;99:389-95) also revealed that the peak frequency of bicoherence around 10 Hz increased when ketamine was added. Because nitrous oxide (N(2)O) and ketamine share several common features, they are often treated as the same category of anesthetic. Here, we investigated the effect of N(2)O on EEG bicoherence and other EEG derivatives during isoflurane anesthesia.
Twenty patients (aged 34-72 years, ASA physical status I and II) of either gender who underwent elective laparoscopic surgery were included. Raw EEG data, along with EEG-derived parameters, were recorded using an A-1050 Bispectral Index (BIS) monitor and our self-authored Bispectral Analyzer for BIS software. We compared 2 peaks of EEG bicoherence (pBIC-low, around 4 Hz; and pBIC-high, around 10 Hz), as well as BIS and spectral edge frequency 95% (SEF95). Anesthesia was induced with 3 mg · kg(-1) thiopental and 3 μg · kg(-1) fentanyl. After tracheal intubation, anesthesia was maintained with isoflurane (expired concentration at 1.0%), oxygen, and nitrogen. Fentanyl was added and maintained at an estimated effect-site concentration of >1.5 ng · mL(-1). We obtained baseline data 1 hour after induction of anesthesia, then 70% N(2)O was added for 30 minutes.
Before N(2)O, pBIC-low and pBIC-high were 49.3% ± 8.3% and 42.4% ± 11.0%. Ten minutes after starting N(2)O, pBIC-high decreased to 14.9% ± 5.9% (P < 0.001), and it was statistically significantly lower throughout the N(2)O period. Meanwhile, pBIC-low transiently decreased to 37.2% ± 12.8% (P = 0.01) during the early phase of N(2)O administration. Before N(2)O, BIS and SEF95 were 43.2 ± 4.9 and 13.1 ± 2.0 Hz, respectively. Both BIS and SEF95 slightly but statistically significantly decreased during N(2)O administration. Fifteen minutes after starting N(2)O, BIS and SEF95 were 35.7 ± 6.2 (P < 0.001) and 8.6 ± 1.8 Hz (P < 0.001) and they decreased more when large δ waves emerged. Fifteen minutes after stopping N(2)O, BIS, SEF95, as well as pBIC-low and pBIC-high returned to pre-N(2)O values.
Dissimilar to the effect of ketamine, N(2)O significantly decreases pBIC-high during isoflurane anesthesia.
Anesthesia and analgesia 05/2012; 115(3):572-7. · 3.08 Impact Factor
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ABSTRACT: Whether effect-site concentrations of propofol (Cep) at loss of consciousness and return of consciousness (LOC and ROC, respectively) in elderly women using Diprifusor are similar is unclear. We investigated whether differences in initial target Cep (Ctarget) alter similarities between Cep values at LOC and ROC.
In this study, female patients (n = 58, age = 72.5 ± 1.1 years) undergoing knee arthroplasty were administered propofol with Diprifusor. Cep at LOC and ROC were estimated for different Ctarget values (3.0-4.5 μg/ml). Pearson's correlation coefficient analysis and simple regression were performed to assess the relationship between Cep at LOC and ROC for each Ctarget. Differences in correlation coefficients of regression lines obtained from each Ctarget group were determined using the t-test.
The different Ctarget groups did not show significant differences in total propofol levels and in Cep values at LOC or ROC. However, Cep at ROC was significantly higher than Cep at LOC when Ctarget was 4.0 and 4.5 μg/ml, whereas these Cep values were not significantly different in low Ctarget groups. Strong positive correlations were observed between Cep at LOC and ROC for all Ctarget groups. Regression coefficients for the different Ctarget groups were not significantly different. Compared to low (≤3.5 μg/ml) Ctarget groups, high Ctarget groups showed significantly shorter time until LOC. Induction quality was not significantly different among the groups.
In elderly women, Cep values at LOC are strong predictors of Cep at ROC when Ctarget is 3.0-4.5 μg/ml. High Ctarget groups (≥4.0 μg/ml) exhibited shorter induction times with normal cardiovascular stability.
Journal of Anaesthesiology Clinical Pharmacology 04/2012; 28(2):194-9.
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ABSTRACT: We investigated whether potentially injurious transpulmonary pressure could be generated by strong spontaneous breathing and exacerbate lung injury even when plateau pressure is limited to <30 cm H2O.
Prospective, randomized, animal study.
University animal research laboratory.
Thirty-two New Zealand White rabbits.
Lavage-injured rabbits were randomly allocated to four groups to receive low or moderate tidal volume ventilation, each combined with weak or strong spontaneous breathing effort. Inspiratory pressure for low tidal volume ventilation was set at 10 cm H2O and tidal volume at 6 mL/kg. For moderate tidal volume ventilation, the values were 20 cm H2O and 7-9 mL/kg. The groups were: low tidal volume ventilation+spontaneous breathingweak, low tidal volume ventilation+spontaneous breathingstrong, moderate tidal volume ventilation+spontaneous breathingweak, and moderate tidal volume ventilation+spontaneous breathingstrong. Each group had the same settings for positive end-expiratory pressure of 8 cm H2O.
Respiratory variables were measured every 60 mins. Distribution of lung aeration and alveolar collapse were histologically evaluated. Low tidal volume ventilation+spontaneous breathingstrong showed the most favorable oxygenation and compliance of respiratory system, and the best lung aeration. By contrast, in moderate tidal volume ventilation+spontaneous breathingstrong, the greatest atelectasis with numerous neutrophils was observed. While we applied settings to maintain plateau pressure at <30 cm H2O in all groups, in moderate tidal volume ventilation+spontaneous breathingstrong, transpulmonary pressure rose >33 cm H2O. Both minute ventilation and respiratory rate were higher in the strong spontaneous breathing groups.
Even when plateau pressure is limited to <30 cm H2O, combined with increased respiratory rate and tidal volume, high transpulmonary pressure generated by strong spontaneous breathing effort can worsen lung injury. When spontaneous breathing is preserved during mechanical ventilation, transpulmonary pressure and tidal volume should be strictly controlled to prevent further lung injury.
Critical care medicine 03/2012; 40(5):1578-85. · 6.37 Impact Factor
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Yukiko Tabuchi,
Tetsuyuki Yasuda,
Hideaki Kaneto,
Tetsuhiro Kitamura,
Junji Kozawa,
Michio Otsuki,
Akihisa Imagawa,
Aya Nakae,
Youichi Matsuda,
Hironobu Uematsu, Takashi Mashimo,
Masahiko Shibata,
Iichiro Shimomura
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ABSTRACT: We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypogonadism was diagnosed to be caused by opioid treatment. Although opioid-induced endocrine dysfunctions are not widely recognized, this case suggests that we should consider the possibility of endocrine dysfunctions in patients with opioid treatment.
Case Reports in Medicine 01/2012; 2012:740603.
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ABSTRACT: The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI).
Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed.
Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation.
The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.
Journal of Anesthesia 06/2011; 25(4):523-30. · 0.83 Impact Factor
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ABSTRACT: Using a model lung connected to six different ventilators, with each ventilator in the airway pressure release ventilation mode, we measured differences in intrinsic positive end-expiratory pressure (PEEPi) during the expiratory phase and calculated the inspiratory and expiratory pressure time product (PTP) as an index of work of breathing during the inspiratory phase.
We compared 6 ventilators: Puritan-Bennett 840, Evita XL, Servo i, Avea, Hamilton G5, and Engström. With a constant inspiratory pressure level of 25 cm H(2)O and expiratory pressure level of 0 cm H(2)O, PEEPi was measured as the expiratory time was decremented from 1.0 second to 0.2 second in steps of 0.1 second. The inspiratory and expiratory PTPs were measured during the ventilator's inspiratory phase by simulating spontaneous breathing with a tidal volume of 300 mL, with a respiratory rate of 30 breaths/min and with expiratory flow rates of 0.5 L/s, 1.0 L/s, and 1.5 L/s.
In all ventilators, the progressive diminution of the expiratory time caused a significant increase in PEEPi (P< 0.001). With a 0.2-second expiratory time, PEEPi ranged from 9.4± 0.07 cm H(2)O for the Servo i to 15.7± 0.04 cm H(2)O for the Avea. The Servo i had a significantly lower inspiratory PTP than did the other ventilators (P< 0.001). When the expiratory flow rate was 0.5 L/s and 1.0 L/s, the expiratory PTP was lower with the Servo i and Evita XL than with the other ventilators (P< 0.001).
PEEPi varied significantly among ventilators. Inspiratory and expiratory work of breathing varied between ventilators when spontaneous breathing occurred during the ventilator's inspiratory phase.
Anesthesia and analgesia 04/2011; 113(3):529-33. · 3.08 Impact Factor
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ABSTRACT: Neuropsychological dysfunction with cardiopulmonary bypass (CPB) may be facilitated by inadequate cerebral oxygen balance during CPB. Olprinone, a phosphodiesterase III inhibitor, augments cerebral blood flow by a direct vasodilator effect on cerebral arteries. We conducted the present randomized study in patients undergoing cardiac surgery with CPB to investigate whether olprinone improved the balance of cerebral oxygen supply and demand during the rewarming period of CPB. After anesthesia, a 5.5 F fiberoptic oximeter catheter was inserted into the right jugular bulb retrogradely for monitoring the jugular venous oxyhemoglobin saturation (SjO2), and a probe of transcranial near-infrared spectroscopy was placed over the forehead for monitoring the bilateral regional cerebral oxygen saturation (rSO2). Patients were randomly assigned to 3 groups, and olprinone was administered at 0, 0.2, or 0.4 μg·kg(-1)·min(-1) after establishment of hypothermic CPB. Olprinone significantly prevented the reduction of the SjO2 at 5 and 10 minutes after the start of rewarming, although it did not alter rSO2. Furthermore, there was a minor reduction of the bilateral rSO2 at low doses of olprinone (0.2 μg·kg(-1)·min(-1)). We conclude that olprinone prevents the decrease of the SjO2 at the rewarming period and improves the balance of cerebral oxygen supply and demand during the rewarming period of CPB. In addition, a future extended study may be required to elucidate the effect of low dose of olprinone.
Journal of cardiovascular pharmacology 02/2011; 57(5):579-83. · 2.83 Impact Factor
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ABSTRACT: Interventions to preserve myocardial function after brain death may increase the donor pool for heart transplantation. The present study using a brain death model of rats was designed to examine the protective potential of nicorandil, an adenosine triphosphate-sensitive potassium channel opener, on myocardial function after brain death.
Rats were anesthetized with sevoflurane. A Fogarty catheter was placed intracranially for induction of brain death. The conductance catheter was inserted into the left ventricle for measurement of myocardial function. Rats were assigned randomly to two groups, one receiving nicorandil before brain death and the other receiving saline (control group). Mean blood pressure, heart rate, maximal rate of rise of left-ventricular pressure and ejection fraction were measured every 30 min for 6h after brain death. The same protocol was performed in the presence of nicorandil combined with 5-hydroxydecanoic acid, a mitochondrial adenosine triphosphate-sensitive potassium channel inhibitor.
Nicorandil temporally, but significantly, improved ejection fraction compared with the control group. Furthermore, 5-hydroxydecanoic acid inhibited the effects of nicorandil.
Nicorandil was effective to preserve ejection fraction after brain death, and myocardial mitochondrial adenosine triphosphate-sensitive potassium channels may be involved in this action.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2011; 40(3):710-4. · 2.40 Impact Factor
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ABSTRACT: This study aimed to investigate the differences in the brain responses between muscle versus skin pain, both of which were caused by tonic mechanical stimuli. Using local anesthesia (LA), we induced muscle pain without any accompanying cutaneous sensation. Subjects underwent functional magnetic resonance imaging while tonic pressure was applied to the right calf under the following four conditions: (1) non-painful pressure without LA (causing mechanoreceptive skin and muscle stimulation); (2) painful pressure without LA (causing nociceptive skin stimulation and mechanoreceptive skin and muscle stimulation); (3) non-painful pressure with LA (causing mechanoreceptive muscle stimulation); (4) painful pressure with LA (causing nociceptive and mechanoreceptive muscle stimulation). Although there was no brain region specifically activated by nociceptive muscle stimuli, activation in the following regions was observed specifically during nociceptive muscle stimuli: anterior midcingulate cortex, anterior and posterior insular cortex, lentiform nucleus, thalamus, pre-supplementary motor area, dorsolateral prefrontal cortex, and inferior parietal lobule. This indicates that there is no region specific for muscle pain but activation pattern or network specific for muscle pain. Furthermore, secondary somatosensory cortex (S2) was found to be responsive to cutaneous pain, not muscle pain, because S2 was specifically activated by nociceptive cutaneous stimuli.
Neuroscience Research 02/2011; 70(1):78-84. · 2.25 Impact Factor
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ABSTRACT: Dendritic cells (DCs), as antigen-presenting cells, play a key role in the induction and regulation of adaptive immune response. Midazolam is reported to have immunomodulatory properties that affect immune cells. However, the effect of midazolam on DCs has not been characterized. We examined the immunomodulatory properties of midazolam on DC-mediated immune response.
After allowing murine bone marrow-derived DCs induced by granulocyte macrophage colony stimulating factor to mature, we analyzed their expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class II molecules, and the secretion of interleukin-12 p40. In vitro, we evaluated the effect of midazolam on maturing DCs in mixed cell cultures containing DCs and T cells. In vivo, we investigated the contact-hypersensitivity response.
Midazolam suppressed the expression of CD80, CD86, and major histocompatibility complex class II molecules from murine DCs. Treated with midazolam, DCs also secreted less interleukin-12 p40. In mixed cell cultures with CD3-positive T cells, midazolam-treated DCs showed less propensity to stimulate the proliferation of CD3-positive T cells and the secretion of interferon-γ from CD4-positive T cells. Midazolam-treated DCs impaired the induction of contact-hypersensitivity response. Treatment with ligands for peripheral benzodiazepine receptor inhibited the up-regulation of CD80 during DC maturation.
Midazolam inhibits the functional maturation of murine DCs and interferes with DC induction of T helper 1 immunity in the whole mouse. In addition, it appears that the immunomodulatory effect of midazolam is mediated via the action of midazolam on the peripheral benzodiazepine receptor.
Anesthesiology 02/2011; 114(2):355-62. · 5.36 Impact Factor
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ABSTRACT: Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.
Journal of Biomedicine and Biotechnology 01/2011; 2011:939023. · 2.44 Impact Factor
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ABSTRACT: High-frequency oscillatory ventilation (HFOV) is thought to protect the lungs of acute respiratory distress syndrome (ARDS) patients. The performance and mechanical characteristics of high-frequency oscillatory ventilators, especially with regard to delivering appropriate tidal volume (V(T)) to compromised lungs, might affect the outcome of patients. We evaluated the performance of two such ventilators using a model lung with a position sensor.
We tested the Metran R100 and SensorMedics 3100B. V(T) was measured using the model lung with the compliance set at 20 or 50 ml/cmH₂O and the resistance at 0 or 20 cmH₂O/l/s. Oscillator frequency was set at 5, 7, and 9 Hz, and amplitude was set at 25%, 50%, 75%, and 100% (100% being maximum amplitude available at each setting configuration).
At each model lung setting, R100 delivered greater V(T) at 5 Hz. V(T) differences between the ventilators decreased as frequency increased and were negligible at 9 Hz. At each model lung setting and frequency, as amplitude increased from 25% to 100%, V(T) increased proportionally more with R100. With an I:E ratio of 1:1, 3100B delivered greater V(T) than with 1:2.
Because it is able to deliver comparably greater V(T), R100 may be a better choice for HFOV in critical ARDS patients. Better proportionality may be a result of more effective amplitude titration for adjusting PaCO₂ during oscillation.
Journal of Anesthesia 12/2010; 24(6):888-92. · 0.83 Impact Factor
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ABSTRACT: It has been reported that the effect of intrathecally administered α2 adrenergic receptor (α2 AR) agonists is enhanced in mice that are chronically tolerant to systemic morphine. However, contributory factors have not been identified. Here we examined whether repeated systemic morphine affected the analgesic potency of intrathecal dexmedetomidine and the expression of subtype A, B and C α2 AR (α2A, α2B and α2C AR) in the dorsal root ganglion and dorsal horn in mice.
After subcutaneous injection of morphine or saline for two weeks, dexmedetomidine was administered intrathecally to evaluate its antinociceptive effect. Also, the α2 AR subtypes and µ-opioid receptor mRNA expression in lumbar dorsal root ganglion was quantified using PCR, and α2A and α2C AR in lumbar dorsal root ganglion and dorsal horn were examined by immunohistochemistry.
Daily morphine enhanced the antinociceptive effect of intrathecal dexmedetomidine, increased all the α2 AR subtypes but decreased the µ-opioid receptor mRNA expression in dorsal root ganglion and increased immunoreactivity of α2A and α2C AR in dorsal root ganglion and dorsal horn.
These results suggest that systemic daily morphine enhances the analgesic effect of intrathecal dexmedetomidine via up-regulation of the α2A, α2B and α2C AR in lumbar dorsal root ganglion and dorsal horn.
The Journal of pharmacy and pharmacology. 12/2010; 62(12):1760-7.
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ABSTRACT: Activation of imidazoline receptors in the central nervous system has protective effect on several types of arrhythmias. We demonstrated that centrally administered rilmenidine, a selective imidazoline receptor agonist, prevented adrenaline-induced arrhythmias during halothane anaesthesia. However, detailed myocardial signaling of the antiarrhythmic effect remains to be unexplored. The present study was designed to examine a role of pertussis toxin-sensitive G protein, phosphatidylinositol 3-kinase/Akt signaling pathway and endogenous nitric oxide in the antiarrhythmic effect of rilmenidine. Male Sprague-Dawley rats were anaesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of adrenaline was defined as the smallest dose producing 3 or more premature ventricular contractions within 15-s period. Firstly, we confirmed that centrally administered rilmenidine prevented adrenaline-induced arrhythmias during halothane anaesthesia and examined the effect of pertussis toxin, wortmannin (a phosphatidylinositol 3-kinase inhibitor), and nitro-L-arginine methyl ester (L-NAME) (a specific nitric oxide synthesis inhibitors), on the antiarrhythmic effect of rilmenidine. We also performed Western blot analysis to determine phosphorylation of Akt and glycogen synthase kinase 3β, a direct Akt downstream target, following the central administration of rilmenidine. The antiarrhythmic effect of rilmenidine was significantly inhibited by pertussis toxin, wortmannin and L-NAME. Rilmenidine increased Akt and glycogen synthase kinase 3β phosphorylation (28±13% and 32±13%, respectively), and this action was abolished by wortmannin. The present results demonstrated that pertussis toxin-sensitive G protein, phosphatidylinositol 3-kinase-Akt-GSK3β signaling pathway and endogenous nitric oxide may play a key role in antiarrhythmic effect of centrally administered rilmenidine.
European journal of pharmacology 11/2010; 647(1-3):155-60. · 2.59 Impact Factor
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ABSTRACT: Peripheral branches of the trigeminal nerve may be damaged during maxillofacial injury or surgical procedures and trigeminal trauma may induce severe pain that is very challenging to treat. Chronic constriction injury to the infraorbital nerve (ION-CCI) by loose ligatures has proven a useful model for some types of trigeminal neuropathic pain disorder. Using ION-CCI rats, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT2C receptors. Allodynia was evaluated by applying von Frey filaments to skin innervated by the injured ION. Dose-dependent antiallodynic effects followed administration of three 5-HT2C receptor agonists, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212: 10, 30, and 100 μg); (S)-2-(chloro-5-fluoro-indol-l-yl)-1-methyamine fumarate (RO 60-0175: 10, 30, and 100 μg); (AaR)-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY-161503: 10, 30, and 100 μg). ED50 values for antiallodynic effects of MK212, RO 60-0175, and WAY-161503 were 39.62, 46.67, and 51.22 μg, respectively. Intrathecal administration of the 5-HT2C receptor antagonist, 8-[5-2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4,5]decane-2,4-dione (RS-102221: 30 μg) did not alter the mechanical threshold. Intrathecal pretreatment with RS-102221 (10 and 30 μg) reduced the antiallodynic effects of the highest dose of 5-HT2C agonists. These results indicated that, in this rat model, the 5-HT2C receptor plays a role in spinal inhibition of trigeminal neuropathic pain.
European journal of pain (London, England) 11/2010; 14(10):999-1006. · 3.37 Impact Factor
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ABSTRACT: Natriuretic peptides exert vasodilatory, natriuretic, and diuretic effects and inhibit renin and aldosterone secretion. Carperitide, a recombinant alpha-human atrial natriuretic peptide (hANP), is used for the treatment of cardiac failure. Patients with renal failure often require renal replacement therapy, and little is known about the pharmacokinetics of carperitide when used for renal replacement therapy.
Eleven patients who received continuous carperitide infusion and needed continuous venovenous hemofiltration (CVVHF) for acute renal failure were observed. The plasma hANP concentration was noted and the hANP clearance during CVVHF was calculated. The results indicated that infused hANP was removed by CVVHF. Although the clearance of hANP by CVVHF was relatively lower than the expected whole body clearance, CVVHF slightly reduced plasma hANP and cyclic guanosine monophosphate concentrations and increased arterial pressure.
CVVHF affects the pharmacology of infused hANP in critically ill patients. Some caution with respect to blood pressure may be necessary when carrying out CVVHF for critically ill patients receiving continuous infusion of natriuretic peptides.
Circulation Journal 09/2010; 74(9):1888-94. · 3.77 Impact Factor
