A pressure-resistant peripherally inserted central catheter is as useful as a central venous catheter for rapid fluid infusion: an in vitro study.

BACKGROUND: Although peripherally inserted central catheters (PICCs) have been widely used, they have not been frequently used in anesthesia practice. The central venous pressure measured via PICCs are reportedly as accurate as that measured via central venous catheters (CVCs), but the findings concerning rapid infusion are unclear. This study examined whether or not pressure-resistant PICCs could be used for rapid fluid infusion.  METHODS: The in-line pressure was measured in similar-sized double-lumen catheters-4-Fr PICC (55, 45 and 35 cm) and 17-G CVC (20 and 13 cm)-at flow rates of saline decided using a roller pump system. We also examined the flow rate at an in-line pressure of 300 mmHg, which is the critical pressure at which hemolysis is considered to occur during blood transfusion. RESULTS: The pressure-resistant PICCs obtained a high flow rate similar to that of CVCs, but the in-line pressures increased in proportion to the flow rate and catheter length. Flow rates at an intra-circuit pressure of 300 mmHg were not significantly different between the 45-cm PICC and 20-cm CVC. CONCLUSION: Pressure-resistant PICCs can be used for rapid fluid infusion.

Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice.

BACKGROUND: Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate CKD. Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. METHODS: To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14-32 weeks old) with proximal tubule-specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. RESULTS: Inducible proximal tubule-specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved GFR, reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. CONCLUSIONS: We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy.

The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation.

Acute cardiorenal syndrome is a common complication of acute cardiovascular disease. Studies of acute kidney injury (AKI) to chronic kidney disease (CKD) transition, including patients suffering acute cardiovascular disease, report high rates of CKD development. Therefore, acute cardiorenal syndrome associates with CKD, but no study has established causation. To define this we used a murine cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) model or sham procedure on male mice. CA was induced with potassium chloride while CPR consisted of chest compressions and epinephrine eight minutes later. Two weeks after AKI was induced by CA/CPR, the measured glomerular filtration rate (GFR) was not different from sham. However, after seven weeks the mice developed CKD, recapitulating clinical observations. One day, and one, two, and seven weeks after CA/CPR, the GFR was measured, and renal tissue sections were evaluated for various indices of injury and inflammation. One day after CA/CPR, acute cardiorenal syndrome was indicated by a significant reduction of the mean GFR (649 in sham, vs. 25 µL/min/100g in CA/CPR animals), KIM-1 positive tubules, and acute tubular necrosis. Renal inflammation developed, with F4/80 positive and CD3-positive cells infiltrating the kidney one day and one week after CA/CPR, respectively. Although there was functional recovery with normalization of GFR two weeks after CA/CPR, deposition of tubulointerstitial matrix proteins α-smooth muscle actin and fibrillin-1 progressed, along with a significantly reduced mean GFR (623 in sham vs. 409 µL/min/100g in CA/CPR animals), proteinuria, increased tissue transforming growth factor-ß, and fibrosis establishing the development of CKD seven weeks after CA/CPR. Thus, murine CA/CPR, a model of acute cardiorenal syndrome, causes an AKI-CKD transition likely due to prolonged renal inflammation.

P2Y12 receptors in primary microglia activate nuclear factor of activated T-cell signaling to induce C-C chemokine 3 expression.

Microglia are widely accepted as surveillants in the central nervous system that are continually searching the local environment for signs of injury. Following an inflammatory situation, microglia alter their morphology, extend ramified processes, and undergo cell body hypertrophy. Extracellular nucleotides are recognized as a danger signal by microglia. ADP acting on P2Y12 receptors induce process extension of microglia thereby attracting microglia to the site of adenosine tri-phosphate/ADP leaking or release. However, the question whether ADP/P2Y12 receptor signaling directly stimulates the production or release of inducible factors such as cytokines remains unclear. In this study, we found that CC chemokine ligand 3 (CCL3) is induced by ADP-treated primary microglia. Pharmacological characterization using pertussis toxin, a P2Y12 receptor inhibitor, and a calcium chelator revealed that CCL3 induction was caused by P2Y12 receptor-mediated intracellular calcium elevation. Next, nuclear factor of activated T-cell dephosphorylation and nuclear translocalization were observed. Calcineurin, an inhibitor for nuclear factor of activated T cell, suppressed CCL3 induction. These data indicate that microglial P2Y12 receptors are utilized to trigger an acute inflammatory response in microglia via rapid CCL3 induction after ADP stimulation.

Differences in anatomical relationship between vertebral artery and internal jugular vein in children and adults measured by ultrasonography.

Cannulation of the internal jugular vein (IJV) under ultrasound guidance can reduce complications, such as common carotid artery (CCA) puncture, accidental vertebral artery (VA) puncture. However, these complications still occur, especially in pediatric patients probably due to anatomical predisposition of VA. This study compared differences in anatomical location of VA and IJV between pediatric and adult patients. Children with body weight <20 kg (n = 16) and adults who required central venous or pulmonary arterial pressure monitoring (n = 21) were enrolled. After induction of general anesthesia and tracheal intubation, patients were positioned for IJV cannulation. Images of the right CCA, IJV and VA were recorded by ultrasonography. The size of each vessel, anatomical relationship of other vessels, distance between vessels and between each vessel and skin were measured. The size of VA relative to IJV was significantly larger in children than in adults (14 vs 7 %, P < 0.001). The absolute and relative distance between IJV and VA were significantly shorter in children than those in adults (P < 0.01). The anatomical relationships between IJV and CCA and that between IJV and VA were not different between children and adults. In children, VA was relatively larger and located closer to IJV than adults. The results call for careful attention to the position of VA during ultrasound-guided IJV cannulation especially in children.

Chemokine (C-C motif) receptor 5 is an important pathological regulator in the development and maintenance of neuropathic pain.

BACKGROUND: The chemokine family has been revealed to be involved in the pathogenesis of neuropathic pain. In this study, the authors investigated the role of chemokine (C-C motif) ligand 3 and its receptors chemokine (C-C motif) receptor 1 and chemokine (C-C motif) receptor (CCR) 5 in neuropathic pain. METHODS: A spinal nerve injury model was established in adult male Wistar rats. The von Frey test and hot plate test were performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry were performed to understand the molecular mechanisms. RESULTS: The expression levels of chemokine (C-C motif) ligand 3 and CCR5 messenger RNA in the spinal cord were up-regulated after nerve injury, which was possibly due to CD11b-positive microglia. Single intrathecal administration of recombinant chemokine (C-C motif) ligand 3 produced biphasic tactile allodynia; each phase of pain behavior was induced by different receptors. Intrathecal injection of CCR5 antagonist suppressed the development of tactile allodynia (12.81 ± 1.33 g vs. 3.52 ± 0.41 g [mean ± SEM, drug vs. control in paw-withdrawal threshold]; P < 0.05, n = 6 each) and could reverse established tactile allodynia (10.87 ± 0.91 g vs. 3.43 ± 0.28 g; P < 0.05, n = 8 and 7). Furthermore, Oral administration of CCR5 antagonist could reverse established tactile allodynia (8.20 ± 1.27 g vs. 3.18 ± 0.46 g; P < 0.05, n = 4 each). CONCLUSIONS: Pharmacological blockade of CCR5 was effective in the treatment of the development and maintenance phases of neuropathic pain. Thus, CCR5 antagonists may be potential new drugs for the treatment of neuropathic pain.

[Acute upper airway obstruction after extubation due to excessive anteflexion of the neck with occipitocervical fusion].

A patient developed upper airway obstruction immediately after tracheal extubation due to excessive anteflexion of the neck with occipitocervical fusion. A 59-year-old woman who had undergone mastectomy 17 years previously was scheduled for occipitocervical fusion for C2 vertebral metastasis. Retroflexion of her neck was restricted. Nasal intubation under sedation was performed using bronchial fiberscopy under fentanyl and propofol anesthesia. Emergence from anesthesia was smooth, and extubation was performed. Immediately after extubation, the patient could not breathe, and manual mask ventilation was impossible. Re-intubation was performed 30 minutes after the extubation. Oral fiberscopy revealed pharyngeal obstruction, and laryngeal edema was not observed. Fixation of her neck in excessive anteflexion was suspected to have caused her dyspnea. Therefore, re-operation was performed, and she was transferred to the intensive care unit under anesthesia. One day postoperatively, extubation was performed successfully with no dyspnea. Fixation of the neck in excessive anteflexion is one of the causes of upper airway obstruction after occipitocervical fusion. We must carefully observe cervical X-ray films to locate the upper airway obstruction, and careful extubation using a tube exchanger is strongly recommended in this operation.

Anesthetic management of cesarean section in a patient with Takayasu's arteritis: a case report.

BACKGROUND: Takayasu's arteritis (TA) is a chronic, progressive, inflammatory arteritis. We presented the case of cesarean section in a patient with TA. CASE PRESENTATION: A 31-year-old pregnant woman with TA underwent a planned cesarean section at 34 weeks of pregnancy. She had stenosis of the cerebral and coronary arteries and heart failure due to aortic regurgitation. Spinal anesthesia was performed. In addition to standard monitoring, arterial blood pressure in the dorsalis pedis artery and regional cerebral tissue oxygen saturation were monitored. Intraoperative arterial blood pressure was maintained using continuous infusion of noradrenaline with a careful intermittent bolus infusion of phenylephrine. All the procedures were successfully performed without significant complications. CONCLUSIONS: In a pregnant woman with TA, severe stenosis of the cerebral and coronary arteries, and heart failure due to valvular heart disease, careful anesthetic management by selecting catecholamines and assessing the perfusion pressure for critical organs is important.

Complete atrio-ventricular block with coronary artery spasm due to direct laryngoscopy in a pediatric patient with laryngeal papillomatosis: a case report.

BACKGROUND: Coronary artery spasm has rarely been reported in pediatric patients. Previous studies have reported comorbidities and risk factors for coronary artery spasms. We present the case of a complete atrio-ventricular (AV) block that occurred in the absence of other risk factors immediately after direct laryngoscopy. CASE PRESENTATION: A 2-year-old girl developed severe coronary artery spasm after direct laryngoscopy for elective laryngeal papillomatosis resection. Immediately after the initiation of laryngoscopy, complete AV block and ST elevation on lead II of the electrocardiogram were observed. These findings indicated that the complete AV block was caused by a right coronary artery spasm. CONCLUSION: Coronary artery spasm resulting in lethal arrhythmia rarely occurs in healthy pediatric patients. To the best of our knowledge, this is the first pediatric case of a severe coronary artery spasm resulting in a complete AV block due to direct laryngoscopy in a healthy patient.

1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report.

BACKGROUND: Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. CASE PRESENTATION: A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. CONCLUSIONS: SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

Cerebral infarction detected after laparoscopic partial hepatectomy: case report.

BACKGROUND: Bleeding and carbon dioxide (CO2) gas embolism have been reported as serious complications associated with laparoscopic surgery. We present a case of cerebral infarction presumably caused by CO2 gas embolism during laparoscopic hepatectomy. CASE PRESENTATION: During liver resection, the end-tidal CO2 suddenly dropped from 40 to 21 mmHg. Simultaneously, ST elevation in lead II and ST depression in lead V5 of the electrocardiogram were observed. After improvement of these electrocardiographic changes, surgery was continued. Postoperatively, incomplete paralysis was present in the right arm and leg. Magnetic resonance imaging revealed cerebral infarction in the broad area of the left cerebral cortex. These complications might have been caused by paradoxical embolism. CONCLUSION: We should always keep in mind the risk of cerebral infarction with neurological deficits in the case of laparoscopic surgery. Careful monitoring and appropriate treatment for gas embolism are necessary during laparoscopic surgery.

Glomerular filtrate proteins in acute cardiorenal syndrome.

Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.

Automated systematic random sampling and Cavalieri stereology of histologic sections demonstrating acute tubular necrosis after cardiac arrest and cardiopulmonary resuscitation in the mouse.

INTRODUCTION: A technical challenge in translational models of kidney injury is determination of the extent of cell death. Histologic sections are commonly analyzed by area morphometry or unbiased stereology, but stereology requires specialized equipment. Therefore, a challenge to rigorous quantification would be addressed by an unbiased stereology tool with reduced equipment dependence. We hypothesized that it would be feasible to build a novel software component which would facilitate unbiased stereologic quantification on scanned slides, and that unbiased stereology would demonstrate greater precision and decreased bias compared with 2D morphometry. MATERIAL AND METHODS: We developed a macro for the widely used image analysis program, Image J, and performed cardiac arrest with cardiopulmonary resuscitation (CA/CPR, a model of acute cardiorenal syndrome) in mice. Fluorojade-B stained kidney sections were analyzed using three methods to quantify cell death: gold standard stereology using a controlled stage and commercially-available software, unbiased stereology using the novel ImageJ macro, and quantitative 2D morphometry also using the novel macro. RESULTS: There was strong agreement between both methods of unbiased stereology (bias -0.004±0.006 with 95% limits of agreement -0.015 to 0.007). 2D morphometry demonstrated poor agreement and significant bias compared to either method of unbiased stereology. CONCLUSION: Unbiased stereology is facilitated by a novel macro for ImageJ and results agree with those obtained using gold-standard methods. Automated 2D morphometry overestimated tubular epithelial cell death and correlated modestly with values obtained from unbiased stereology. These results support widespread use of unbiased stereology for analysis of histologic outcomes of injury models.

Micropuncture of Bowman's Space in Mice Facilitated by 2 Photon Microscopy.

Renal micropuncture and renal 2-photon imaging are seminal techniques in renal physiology. However, micropuncture is limited by dependence on conventional microscopy to surface nephron features, and 2-photon studies are limited in that interventions can only be assessed at the organ, rather than the nephron level. In particular, micropuncture studies of the glomeruli of mice have been challenged by the paucity of surface glomeruli in mice. To address this limitation in order to pursue studies of aspirate from Bowman's space in mouse physiologic models, we developed 2-photon glomerular micropuncture. We present a novel surgical preparation that allows lateral access to the kidney while preserving the required vertical imaging column for 2-photon microscopy. Administration of high molecular weight fluorescein isothiocyanate (FITC)-dextran is used to render the renal vasculature and therefore glomeruli visible for 2-photon imaging. A quantum dot-coated pipette is then introduced under stereotactic guidance to a glomerulus selected from the several to many which may be visualized within the imaging window. In this protocol, we provide details of the preparation, materials, and methods necessary to carry out the procedure. This technique facilitates previously-impossible physiologic study of the kidney, including recovery of filtrate from Bowman's space and all segments of the nephron within the imaging depth limit, about 100 µm below the renal capsule. Pressure, charge and flow may all be measured using the introduced pipette. Here, we provide representative data from liquid chromatography/mass spectrometry performed on aspirate from Bowman's space. We expect this technique to have wide applicability in renal physiologic investigation.

Optogenetic Activation of Non-Nociceptive Aß Fibers Induces Neuropathic Pain-Like Sensory and Emotional Behaviors after Nerve Injury in Rats.

Neuropathic pain is caused by peripheral nerve injury (PNI). One hallmark symptom is allodynia (pain caused by normally innocuous stimuli), but its mechanistic underpinning remains elusive. Notably, whether selective stimulation of non-nociceptive primary afferent Aß fibers indeed evokes neuropathic pain-like sensory and emotional behaviors after PNI is unknown, because of the lack of tools to manipulate Aß fiber function in awake, freely moving animals. In this study, we used a transgenic rat line that enables stimulation of non-nociceptive Aß fibers by a light-activated channel (channelrhodopsin-2; ChR2). We found that illuminating light to the plantar skin of these rats with PNI elicited pain-like withdrawal behaviors that were resistant to morphine. Light illumination to the skin of PNI rats increased the number of spinal dorsal horn (SDH) Lamina I neurons positive to activity markers (c-Fos and phosphorylated extracellular signal-regulated protein kinase; pERK). Whole-cell recording revealed that optogenetic Aß fiber stimulation after PNI caused excitation of Lamina I neurons, which were normally silent by this stimulation. Moreover, illuminating the hindpaw of PNI rats resulted in activation of central amygdaloid neurons and produced an aversion to illumination. Thus, these findings provide the first evidence that optogenetic activation of primary afferent Aß fibers in PNI rats produces excitation of Lamina I neurons and neuropathic pain-like behaviors that were resistant to morphine treatment. This approach may provide a new path for investigating circuits and behaviors of Aß fiber-mediated neuropathic allodynia with sensory and emotional aspects after PNI and for discovering novel drugs to treat neuropathic pain.

Incidental Cerebral Acute Subdural Hematoma After Transforaminal Lumbar Interbody Fusion: A Case Report.

We present a 68-year-old woman who developed acute cerebral subdural hematoma (SDH) early after transforaminal lumbar interbody fusion. Four hours postoperatively, the patient complained of headache and nausea. Enhanced cranial computed tomography showed cerebral SDH. Despite no obvious intraoperative dural damage, we suggest that cerebrospinal fluid leakage by incidental dural tear likely caused the SDH. To our knowledge, this is the first report of detected cerebral SDH immediately after spinal surgery in spite of no neurological deficits.