Κυριακή, 4 Μαρτίου 2018

Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice

Abstract

Purpose

Nicorandil has dual properties and acts as a nitric oxide donor and an ATP-sensitive potassium (KATP) channel opener. Considering its pharmacological profile, nicorandil might exert protective effects on the brain as well as on the heart. The purpose of this study was to directly evaluate the effect of nicorandil on cerebral blood flow (CBF) in mice using a transcranial Doppler method.

Methods

Under general anesthesia, the nicorandil groups received a single-bolus intraperitoneal injection of the respective doses of nicorandil (1, 5, or 10 mg/kg), while the control group received vehicle only. CBF was measured using a transcranial Doppler flowmeter. NG-nitro-l-arginine methyl ester and glibenclamide were used to elucidate the underlying mechanisms.

Results

A single-bolus injection of 1 mg/kg of nicorandil increased the CBF (11.6 ± 3.6 vs. 0.5 ± 0.7%, p < 0.001) without affecting the heart rate and blood pressure. On the contrary, 5 and 10 mg/kg of nicorandil significantly decreased the cerebral blood flow by decreasing the mean blood pressure below the cerebral autoregulation range. The positive effect of 1 mg/kg of nicorandil on the cerebral blood flow was inhibited by co-administration of either NG-nitro-l-arginine methyl ester or glibenclamide.

Conclusions

A clinical dose of nicorandil increases CBF without affecting systemic hemodynamics. The positive effect of nicorandil on CBF is most likely caused via both the nitric oxide pathway and KATP channel opening.



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Comparative genomics: Blood, guts and vampire bats



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The vulnerability of spinal motoneurons and soma size plasticity in a mouse model of amyotrophic lateral sclerosis

Abstract

Alpha-motoneuron soma size is correlated with the cell's excitability and function, and has been posited as a plastic property that changes during cellular maturation, injury, and disease. This study examined whether alpha-motoneuron somas change in size over disease progression in the G93A mouse model of amyotrophic lateral sclerosis (ALS), a disease characterized by progressive motoneuron death. We used 2D- and 3D-morphometric analysis of motoneuron size and measures of cell density at four key disease stages: Neonatal, P10 – with earliest known disease changes; young adult, P30 – presymptomatic with early motoneuron death; symptom onset, P90 – with death of 70–80% of motoneurons; and end-stage, P120+ – with full paralysis of hindlimbs. We additionally examined differences in lumbar vs. sacral vs. cervical motoneurons; in motoneurons from male vs. female mice; and in fast vs. slow motoneurons. We present the first evidence of plastic changes in the soma size of spinal α-motoneurons occurring throughout different stages of ALS with profound effects on motoneuron excitability. Somatic changes are time-dependent and are characterized by early-stage enlargement (P10 and P30); no change around symptom onset; and shrinkage at end-stage. A key finding in the study indicates that disease-vulnerable motoneurons exhibit increased soma sizes (P10 and P30). This pattern was confirmed across spinal cord regions, genders, and motoneuron types. This extends the theory of motoneuron size-based vulnerability in ALS: not only are larger motoneurons more vulnerable to death in ALS, but are also enlarged further in the disease. Such information is valuable for identifying ALS pathogenesis mechanisms.

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Virtual reality rehabilitation with functional electrical stimulation improves upper extremity function in patients with chronic stroke: a pilot randomized controlled study

Publication date: Available online 2 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Hyeyoung Lee, Ji-Yeong Lee, Mi-Young Kim, Yu-Jin Jeon, Suyoung Kim, Joon-Ho Shin
ObjectiveTo compare virtual reality (VR) combined with functional electrical stimulation (FES) to cyclic FES for improving upper extremity function and health-related quality of life in patients with a chronic stroke.DesignA pilot, randomized, single blinded, controlled trial.SettingStroke rehabilitation inpatient unitParticipantsForty-eight participants with a hemiplegia secondary to a unilateral stroke for >3 months, with a hemiplegic wrist extensor Medical Research Council (MRC) scale score of 1–3.InterventionsFES was applied to the wrist extensors and finger extensors. A virtual-reality(VR) based wearable rehabilitation device was used, combined with FES and virtual activity-based training. The control group received cyclic FES only. Both groups completed 20 sessions, over a 4-week period.Main outcome measuresPrimary outcomes were the change in the Fugl–Meyer Assessment: upper extremity (FMA) and Wolf Motor Function Test (WMFT) scores. Secondary outcomes were the change in the Box and Block test (BB), Jebsen Taylor Hand Function Test (JTT), and Stroke Impact Scale (SIS) scores. Assessments were performed at baseline (T0) and at 2 weeks (T1), 4 weeks (T4), and 8 weeks (T8). Between-group comparisons were evaluated using a repeated measures analysis of variance.ResultsForty-one participants were included in the analysis. Compared to FES alone, VR-FES produced greater increase in FMA–distal score (p=0.011) and marginal improvement in JTT–gross score (p=0.057). VR-FES produced greater, although non-significant, improvements in all other outcome measures, except in the SIS–ADL/IADL score.ConclusionsFES with VR-based rehabilitation may be more effective than cyclic FES to improve distal gross upper extremity function post-stroke.



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Gait Training in Acute Spinal Cord Injury Rehabilitation – Utilization and Outcomes Among Non-Ambulatory Individuals: Findings from the SCIRehab Project

Publication date: Available online 3 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Rigot, Lynn Worobey, Michael L. Boninger
ObjectivesTo investigate relation of gait training (GT) during inpatient rehabilitation (IPR) to outcomes of people with traumatic spinal cord injury (SCI).DesignProspective observational study using the SCIRehab database.SettingSix IPR facilities.ParticipantsPatients with new SCI receiving initial rehabilitation (n=1376).InterventionsPatients were divided into groups of who did and did not receive GT. Patients were further subdivided based on their primary mode of mobility as measured by the Functional Independence Measure (FIM).Outcome MeasuresPain rating scales; Patient Health Questionnaire Mood Subscale; Satisfaction with Life Scale (SWLS); and Craig Handicap Assessment and Reporting Technique (CHART).ResultsNearly 58% of all patients received GT, including 33.3% of patients who were primarily using a wheelchair 1-year after discharge from IPR. Those who used a wheelchair and received GT, received significantly less transfer and wheeled mobility training (p<.001). CHART physical independence (p=.002), mobility (p=.024), and occupation (p=.003) scores were significantly worse in patients who used a wheelchair at 1-year and received GT, compared to those who used a wheelchair and did not receive GT in IPR. Older age was also a significant predictor of worse participation as measured by the CHART.ConclusionsA significant percentage of individuals who are not likely to become functional ambulators are spending portions of their IPR stays performing GT, which is associated with less time allotted for other functional interventions. GT in IPR was also associated with participation deficits at 1-year for those who used a wheelchair, implying the potential consequences of opportunity costs, pain, and psychological difficulties of receiving unsuccessful GT. Clinicians should consider this data when deciding to implement gait training during initial inpatient rehabilitation.



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Effects of Intraneural Injection of Dexmedetomidine in Combination With Ropivacaine in Rat Sciatic Nerve Block

Background and Objectives Dexmedetomidine is known to have neural protection effect via attenuation of inflammatory responses induced by local anesthetics. We investigated whether intraneural dexmedetomidine is effective for attenuating or preventing neural injury resulting from inadvertent intraneural injection of local anesthetic. Methods Rats were randomly divided, and left sciatic nerve was surgically exposed. The rats received no injection (control group) or intraneural injections of 0.2 mL of normal saline (saline group), 0.2 mL of 0.5% ropivacaine (ropivacaine group), or 0.2 mL of 0.5% ropivacaine and 0.5 μg/kg of dexmedetomidine (ropivacaine plus dexmedetomidine group). Interleukin (IL)-6 and IL-1β messenger RNA (mRNA) levels were detected at 60 minutes after intraneural injection in experiment 1 (5 per group). Sensory and motor functions were assessed until the return of normal sensory and motor functions, and histopathological and ultrastructure analysis were performed at 4 weeks after intraneural injection in experiment 2 (8 per group). Results Dexmedetomidine with ropivacaine better enhanced sensory and motor blockade than ropivacaine alone. IL-6 (3.2 ± 1.0 vs 5.9 ± 2.1), IL-1β (1.1 ± 0.1 vs 2.2 ± 0.7) levels, scores of axon and myelinated fiber degeneration (1 [0–2] vs 2 [1–3]), and demyelinated fiber percentages (20.1 ± 10.4 vs 48.3 ± 12.7) were lower in the ropivacaine plus dexmedetomidine group than in the ropivacaine group. No animals showed any signs of permanent neurological deficit. Conclusions Intraneural dexmedetomidine has sensory and motor blockade-enhancing effects, anti-inflammatory properties, and protective effects against neural injury. These findings suggest that dexmedetomidine as an adjuvant has beneficial effects in rat when intraneural injection of local anesthetic occurs. Accepted for publication October 4, 2017. Address correspondence to: Deok-hee Lee, MD, PhD, Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University, 170, Hyeonchung-ro, Nam-gu, Daegu, Republic of Korea (e-mail: dhlee415@ynu.ac.kr). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Intraoperative Neuromonitoring During Sciatic Nerve Schwanomma Excision: Utility of Evoked Potentials

No abstract available

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Renal Interstitial Exhaustion and SGLT2 Blockers

No abstract available

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Pulse Pressure and Carotid Artery Doppler Velocimetry as Indicators of Maternal Volume Status: A Prospective Cohort Study

BACKGROUND: Narrow pulse pressure has been demonstrated to indicate low central volume status. In critically ill patients, volume status can be qualitatively evaluated using Doppler velocimetry to assess hemodynamic changes in the carotid artery in response to autotransfusion with passive leg raise (PLR). Neither parameter has been prospectively evaluated in an obstetric population. The objective of this study was to determine if pulse pressure could predict the response to autotransfusion using carotid artery Doppler in healthy intrapartum women. We hypothesized that the carotid artery Doppler response to PLR would be greater in women with a narrow pulse pressure, indicating relative hypovolemia. METHODS: Intrapartum women with singleton gestations ≥35 weeks without acute or chronic medical conditions were recruited to this prospective cohort study. Participants were grouped by admission pulse pressure as

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The Amazing Language of Medicine: Understanding Medical Terms and Their Backstories

No abstract available

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The Effect of Repeated Versus Initial Procalcitonin Measurements on Diagnosis of Infection in the Intensive Care Setting: A Prospective Observational Study

Procalcitonin (PCT) measurement has been proposed to direct antibiotic use. We examined whether repeated PCT measurements (0, 6, and/or 12 hours) versus the initial measurement only (time 0) increased the sensitivity and specificity of PCT for diagnosing infection in intensive care unit patients. Infection was identified in 67/176 (38%) patients. The sensitivity of repeated versus the initial PCT measurement (with a cutoff value 0.5 ng/mL) was 52/67 (77%; 95% confidence interval [CI], 66%–87%) vs 46/67 (69%; 95% CI, 56%–79%; P = .04) and specificity 60/109 (55%; 95% CI, 45%–65%) vs 59/109 (54%; 95% CI, 44%–64%; P = 1.0). Repeat PCT evaluations over 12 hours did not provide a clinically significant improvement in diagnostic accuracy when compared to the initial single test. Accepted for publication January 17, 2018. P. D. Levin and M. J. Cohen contributed equally to this article. Funding: This study was supported by Brahms and Siemens, which provided the procalcitonin kits at no cost. The authors declare no conflicts of interest. The information in this study was presented in part at the European Society of Intensive Care Medicine (ESICM) 27th Annual Congress, Barcelona, 2014. Reprints will not be available from the authors. Address correspondence to Shmuel Benenson, MD, MSc, Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 9112001, Israel. Address e-mail to Benenson@Hadassah.org.il. © 2018 International Anesthesia Research Society

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Description of a Novel Set-Up for Functional Echocardiographic Assessment of Left Ventricular Performance During Ex Vivo Heart Perfusion

Ex vivo heart perfusion (EVHP) is a new technology aimed at decreasing cold ischemia time and evaluating cardiac function before transplanting a donor heart. In an experimental EVHP swine model, we tested a 3D-printed custom-made set-up to perform surface echocardiography on an isolated beating heart during left ventricular loading. The views obtained at any time point were equivalent to standard transesophageal and transthoracic views. A decrease in left ventricular function during EVHP was observed in all experiments. Accepted for publication December 29, 2017. Funding: This study was supported by the Peter Munk Cardiac Foundation, private donation, and the University of Toronto Anesthesia Merit Award. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Massimiliano Meineri, MD, FASE, Department of Anesthesia, Toronto General Hospital, 200 Elizabeth St EN 3–442, Toronto, ON, M5G 2C4, Canada. Address e-mail to Massimiliano.Meineri@uhn.ca. © 2018 International Anesthesia Research Society

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The Association of Targeted Cell Salvage Blood Transfusion During Cesarean Delivery With Allogeneic Packed Red Blood Cell Transfusions in a Maternity Hospital in China

BACKGROUND: Autologous transfusion of intraoperative cell salvage blood may be a potential method to decrease the need for allogeneic packed red blood cell transfusions after cesarean delivery, although there are limited data on the benefits of this method. This study evaluated the implementation of targeted intraoperative cell salvage during cesarean delivery in women at increased risk for hemorrhage at the Women's and Children's Hospital in Ningbo, China. METHODS: All women who underwent cesarean delivery >28 weeks of gestation were included in the study. The period before intraoperative cell collection (October 1, 2010, to August 31, 2012, n = 11,322) was compared with the postimplementation period (September 1, 2012, to June 30, 2015, n = 17,456) using an interrupted time series analysis. In the postimplementation period, women suspected to be at increased risk of the need for a blood transfusion (1604, 9.2%) underwent intraoperative cell salvage collection. The primary outcomes were the monthly rate of allogeneic packed red blood cell use and the incidence of clinical manifestation of acute blood transfusion reactions. RESULTS: The mean (standard deviation) estimated monthly allogeneic packed blood cell transfusion rate at the end of the 57-month study was 2.2% ± 0.7% with the implementation compared with 2.7% ± 0.9% without, difference −0.5%, 95% CI, −1.4% to 0.3%; P = .22. The mean number of allogeneic units transfused per patient was 4.1 ± 0.4 units with implementation and 3.9 ± 0.9 units without, difference 0.2, 95% CI, −1.7 to 1.1 units; P = .69. Intraoperative cell salvage blood was reinfused in 757 (47%) and wasted in 847 (53%) cases. The monthly intraoperative allogeneic packed red blood cells use rate was lower after implementation (difference −0.7%, 95% CI, −0.1% to −1.4%; P = .03); however, the monthly postpartum allogeneic packed red blood cell use rate was unchanged (difference −0.2%, 95% CI, −0.4% to 0.7%; P = .56). The clinical manifestation of acute blood transfusion reactions rate was unchanged (difference −2%, 99% CI, −9% to 5%; P = .55) between the periods. CONCLUSIONS: Our findings suggest that targeted intraoperative cell salvage in women undergoing cesarean delivery was associated with less allogeneic blood exposure in the operating room, but not in the postoperative period. Intraoperative cell salvage in targeted cesarean deliveries was not associated with a lesser allogeneic red blood cell exposure over the hospital admission period. The lack of adverse events associated with intraoperative cell salvage supports the safety of intraoperative cell salvage in cesarean delivery. Accepted for publication January 8, 2018. Funding: None. R. J. McCarthy is currently affiliated with the Department of Anesthesiology, Rush University Medical Center, Chicago, Illinois. Conflicts of Interest: See Disclosures at the end of the article. The study was presented at the 2015 Annual Meeting of the American Society of Anesthesiologists, October 24–28, San Diego, CA. Reprints will not be available from the authors. Address correspondence to Robert J. McCarthy, PharmD, Department of Anesthesiology, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612. Address e-mail to robert_j_mccarthy@rush.edu. © 2018 International Anesthesia Research Society

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Acute Respiratory Distress Syndrome

No abstract available

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Predicting Persistent Pain After Surgery: Can Predicting the Weather Serve as an Example?

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Excipients in Anesthesia Medications

Medications used in anesthesiology contain both pharmacologically active compounds and additional additives that are usually regarded as being pharmacologically inactive. These additives, called excipients, serve diverse functions. Despite being labeled inert, excipients are not necessarily benign substances. Anesthesiologists should have a clear understanding of their chemical properties and the potential for adverse reactions. This report catalogs the excipients found in drugs commonly used in anesthesiology, provides a brief description of their function, and documents examples from the literature regarding their adverse effects. Accepted for publication January 8, 2018. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Funding: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Mark A. Burbridge, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94304. Address e-mail to markburb@stanford.edu. © 2018 International Anesthesia Research Society

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A Device for the Quantification of Oxygen Consumption and Caloric Expenditure in the Neonatal Range

BACKGROUND: The accurate measurement of oxygen consumption (VO2) and energy expenditure (EE) may be helpful to optimize the treatment of critically ill patients. However, current techniques are limited in their ability to accurately quantify these end points in infants due to a low VO2, low tidal volume, and rapid respiratory rate. This study describes and validates a new device intended to perform in this size range. METHODS: We created a customized device that quantifies inspiratory volume using a pneumotachometer and concentrations of oxygen and carbon dioxide gas in the inspiratory and expiratory limbs. We created a customized algorithm to achieve precise time alignment of these measures, incorporating bias flow and compliance factors. The device was validated in 3 ways. First, we infused a certified gas mixture (50% oxygen/50% carbon dioxide) into an artificial lung circuit, comparing measured with simulated VO2 and carbon dioxide production (VCO2) within a matrix of varying tidal volume (4–20 mL), respiratory rate (20–80 bpm), and fraction of inspired oxygen (0.21–0.8). Second, VO2, VCO2, and EE were measured in Sprague Dawley rats under mechanical ventilation and were compared to simultaneous Douglas bag collections. Third, the device was studied on n = 14 intubated, spontaneously breathing neonates and infants, comparing measured values to Douglas measurements. In all cases, we assessed for difference between the device and reference standard by linear regression and Bland–Altman analysis. RESULTS: In vitro, the mean ± standard deviation difference between the measured and reference standard VO2 was +0.04 ± 1.10 (95% limits of agreement, −2.11 to +2.20) mL/min and VCO2 was +0.26 ± 0.31 (−0.36 to +0.89) mL/min; differences were similar at each respiratory rate and tidal volume measured, but higher at fraction of inspired oxygen of 0.8 than at 0.7 or lower. In rodents, the mean difference was −0.20 ± 0.55 (−1.28 to +0.89) mL/min for VO2, +0.16 ± 0.25 (−0.32 to +0.65) mL/min for VCO2, and −0.84 ± 3.29 (−7.30 to +5.61) kcal/d for EE. In infants, the mean VO2 was 9.0 ± 2.5 mL/kg/min by Douglas method and was accurately measured by the device (bias, +0.22 ± 0.87 [−1.49 to +1.93] mL/kg/min). The average VCO2 was 8.1 ± 2.3 mL/kg/min, and the device exhibited a bias of +0.33 ± 0.82 (−1.27 to +1.94) mL/kg/min. Mean bias was +2.56% ± 11.60% of the reading for VO2 and +4.25% ± 11.20% of the reading for VCO2; among 56 replicates, 6 measurements fell outside of the 20% error range, and no patient had >1 of 4 replicates with a >20% error in either VO2 or VCO2. CONCLUSIONS: This device can measure VO2, VCO2, and EE with sufficient accuracy for clinical decision-making within the neonatal and pediatric size range, including in the setting of tachypnea or hyperoxia. Accepted for publication January 5, 2018. Funding: This work was supported by grants from the Gerber Foundation, Hess Family Philanthropic Fund, and the Boston Children's Hospital Heart Center Strategic Investment Fund. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Boston Children's Hospital (B. D. Polizzotti and J. N. Kheir) and InnoCC (P. Clemensen.) are in the process of filing a patent entitled "Oxygen Consumption and Energy Expenditure Monitoring in Infants and Children" describing the methods described herein. Clinical trial registry number: NCT03154112; http://ift.tt/2FfBHI0. Reprints will not be available from the authors. Address correspondence to John N. Kheir, MD, Department of Cardiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115. Address e-mail to john.kheir@childrens.harvard.edu. © 2018 International Anesthesia Research Society

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Pain Medicine: An Essential Review

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In Response

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Questions Regarding Perioperative Surgical Home by Kim et al

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In Response

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