BK channel dysfunction disrupts attention-controlled behaviors and altered perseverative responses in murine instrumental learning.

This study examined the effect of knockout of KCNMA1 gene, coding for the BK channel, on cognitive and attentional functions in mice, with an aim to better understand its implications for human neurodevelopmental disorders. The study used the 3-choice serial reaction time task (3-CSRTT) to assess the learning performance, attentional abilities, and repetitive behaviors in mice lacking the KCNMA1 gene (KCNMA1-/-) compared to wild-type (WT) controls. Results showed no significant differences in learning accuracy between the two groups. However, KCNMA1-/- mice were more prone to omitting responses to stimuli. In addition, when the timing of cue presentation was randomized, the KCNMA1-/- showed premature responses. Notably, these mice also demonstrated a marked reduction in perseverative responses, which include repeated nose-poke behaviors following decisions. These findings highlight the involvement of the KCNMA1 gene in managing attention, impulsivity, and potentially moderating repetitive actions.

Cerebral oxygenation saturation in childhood: difference by age and comparison of two cerebral oximetry algorithms.

Few reports are available on the monitoring of regional cerebral oxygen saturation (rSO2) in pediatric patients undergoing non-cardiac surgical procedures. In addition, no study has examined the rSO2 levels in children of a broad age range. In this study, we aimed to assess and compare rSO2 levels in pediatric patients of different age groups undergoing non-cardiac surgery. We used two oximeters, tNIRS-1, which uses time-resolved spectroscopy, and conventional INVOS 5100C. Seventy-eight children-26 infants, 26 toddlers, and 26 schoolchildren-undergoing non-cardiac surgery were included. We investigated the differences in the rSO2 levels among the age groups and the correlation between the models and physiological factors influencing the rSO2 values. rSO2 measured by INVOS 5100C was significantly lower in infants than those in other patients. rSO2 measured by tNIRS-1 was higher in the toddler group than those in the other groups. The rSO2 values of tNIRS-1 and INVOS 5100C were moderately correlated (r = 0.41); however, those of INVOS 5100C were approximately 20% higher, and a ceiling effect was observed. The values in INVOS 5100C and tNIRS-1 were affected by blood pressure and the minimum alveolar concentration of sevoflurane, respectively. In pediatric patients undergoing non-cardiac surgery, rSO2 values differed across the three age groups, and the pattern of these differences varied between the two oximeters employing different algorithms. Further research must be conducted to clarify cerebral oxygenation in children.

Trigeminal Sensitization in a Closed Head Model for Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is often accompanied by neurological and ocular symptoms that involve trigeminal nerve pathways. Laser-induced shock wave (LISW) was applied to the skull of male rats as a model for mTBI, while behavioral and neural recording methods were used to assess trigeminal function. The LISW caused greater eye wiping behavior to ocular instillation of hypertonic saline (Sham = 4.83 ± 0.65 wipes/5 min, LISW = 12.71 ± 1.89 wipes/5 min, p < 0.01) and a marked reduction in the time spent in bright light consistent with enhanced periocular and intraocular hypersensitivity, respectively (Sham = 16.3 ± 5.6 s, LISW = 115.5 ± 27.3 s, p < 0.01). To address the early neural mechanisms of mTBI, single trigeminal brainstem neurons, identified by activation to corneal or dural mechanical stimulation, were recorded in trigeminal subnucleus interpolaris/caudalis (Vi/Vc) and trigeminal subnucleus caudalis/upper cervical cord (Vc/C1) regions. The LISW caused marked sensitization to hypertonic saline and to exposure to bright light in neurons of both regions (p < 0.05). Laser speckle imaging revealed an increase in meningeal arterial blood flow to bright light after LISW (Sham = 4.7 ± 2.0 s, LISW = 469.0 ± 37.9 s, p < 0.001). Local inhibition of synaptic activity at Vi/Vc, but not at Vc/C1, by microinjection of CoCl2, prevented light-evoked increases in meningeal blood flow in LISW-treated rats. By contrast, topical meningeal application of phenylephrine significantly reduced light-evoked responses of Vi/Vc and Vc/C1 neurons. These data suggested that neurons in both regions became sensitized after LISW and were responsive to changes in meningeal blood flow. Neurons at the Vi/Vc transition and at Vc/C1, however, likely serve different roles in mediating the neurovascular and sensory aspects of mTBI.

Differences of cerebral oxygen saturation in dialysis patients: a comparison of three principals of near infrared spectroscopy.

PURPOSE: It has been reported that cerebral oxygen saturation (rSO2) measured by near infrared spectroscopy is low in dialysis patients. We compared the rSO2 values of dialysis patients before living donor kidney transplantation and their donors as controls by using three spectroscopes that utilize different principals, the INVOS 5100C (spatially resolved spectroscopy), FORE-SIGHT ELITE (modified Beer-Lambert law) and tNIRS-1 (time-resolved spectroscopy). METHODS: Before induction of anesthesia, the sensors of one of the three spectroscopes were placed on the forehead and rSO2 values were recorded followed by the same measurement using the other two spectroscopes. The primary objective was to compare the rSO2 values of the dialysis patients and controls using the three spectroscopes by the unpaired t test. Then we compared the rSO2 values among the spectroscopes in both dialysis patients and controls by one-way ANOVA. Finally, we examined the relations between the rSO2 values and the physiological values by using the Pearson correlation coefficient. RESULTS: Fifteen pairs of dialysis patients and controls were studied. With the INVOS 5100 C, the values of the dialysis patients (59.7 ± 9.7% (mean ± standard deviation) were 13% lower than those of the controls (73.3 ± 6.9%) (P < 0.01). With the tNIRS-1, the values were 57.8 ± 4.8% in the dialysis patients and 63.3 ± 3.5% in the controls (P < 0.01). Almost no differences were observed with the FORE-SIGHT ELITE (71.6 ± 4.9% [dialysis patients] vs. 70.8 ± 4.3% [Controls]) (P = 0.62). Among the spectroscopes, the values were significantly different in both dialysis patients and controls. For the INVOS 5100C and tNIRS-1, correlation coefficients between rSO2 values and blood Hb and serum Alb were more than 0.5. CONCLUSIONS: The rSO2 values for comparisons between the dialysis patients and the controls were different according to differences of the principles of the near infrared spectroscopes. In the INVOS 5100C and tNIRS-1, rSO2 values may be related to blood Hb and serum Alb.

Factors Affecting Transcranial Motor-Evoked Potential Measurements Using Single-Train Stimulation with an Increased Number of Pulses during Adolescent Scoliosis Surgery: A Prospective Observational Study.

Measurement of transcranial motor-evoked potentials (TcMEPs) during scoliosis surgery helps detect postoperative new neurological defects. However, TcMEP interpretation is difficult owing to the influence of intraoperative physiological, pharmacological, and time-related factors as well as stimulation conditions. In this study, we aimed to investigate the effect of the abovementioned factors on TcMEP amplitude using single-train stimulation with an increased number of pulses (STS-INP) during adolescent scoliosis surgery; moreover, we evaluated the complications of TcMEP measurement. We included 50 patients and 706 TcMEP measurements. A total of 1412 TcMEP waveforms were analyzed, each on the bilateral abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles. We estimated the mean difference (95% confidence interval (CI)) and predicted mean difference (95% CI) evaluated using the interquartile range of each factor, based on a mixed-effect model with random intercepts for TcMEP amplitude. The predicted mean differences in TcMEP amplitude were clinically small compared with the actual TcMEP amplitude, suggesting that each factor had a limited effect on TcMEP amplitude. No intraoperative bite injuries or seizures were observed. Using STS-INP during adolescent scoliosis surgery may enable accurate measurement of TcMEP amplitude with neither complications nor the influence of various intraoperative factors.

Acquired laryngomalacia as a cause of post-extubation stridor and extubation failure following craniotomy: a case report.

BACKGROUND: Laryngomalacia is a dynamic airway condition characterized by flaccid laryngeal tissue and inward collapse of supraglottic structures during inspiration. Although it may cause airway obstruction and requires careful management, there have been few reports regarding laryngomalacia after surgery. We report a case of adult-onset laryngomalacia occurred after craniotomy requiring reintubation. CASE PRESENTATION: A 21-year-old man was admitted to the ICU after craniotomy for a cerebellopontine angle tumor. He developed severe stridor immediately after extubation on the postoperative day 2 and required reintubation. On the postoperative day 5, similar episode occurred following re-extubation and fiberoptic laryngoscopy revealed a collapsed epiglottis and left arytenoid into the glottis. A diagnosis of laryngomalacia was made, and he underwent tracheostomy. Laryngomalacia had completely improved; however, bilateral vocal cord paralysis was detected 2 weeks later. CONCLUSIONS: Acquired laryngomalacia should be considered as a possible mechanism of the airway symptoms in a patient with neurological dysfunction.

Chronological changes in plasma levobupivacaine concentrations after bilateral modified thoracoabdominal nerve block through perichondrial approach.

The local anesthetic (LA) systemic toxicity of trunk blocks is a major concern. Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has attracted attention; however, plasma LA level is unknown. We tested whether the peak plasma LA concentration following M-TAPA, using 25 mL of 0.25% levobupivacaine mixed with epinephrine on each side, would be below the toxic level (2.6 µg/mL). We recruited 10 patients undergoing abdominal surgery with planned M-TAPA between November 2021 and February 2022. In all patients, 25 mL of 0.25% levobupivacaine mixed with 1:200,000 epinephrine was administered on each side. Blood samples were obtained at 10, 20, 30, 45, 60, and 120 min after the block. The highest individual peak and the mean peak plasma LA concentrations were 1.03 and 0.73 µg/mL, respectively. We could not capture the peak in five patients; however, the highest concentrations in all patients were significantly lower than the toxic level. A negative correlation between the peak level and body weight was observed. Our results indicated that the plasma LA concentration following M-TAPA using total of 50 mL of 0.25% levobupivacaine with epinephrine remains below the toxic level. Further research is required due to the small sample size of this study.Trial registry number: UMIN000045406.

The comparison of postoperative analgesic requirements between modified thoracoabdominal nerve block through perichondrial approach versus wound infiltration analgesia in patients undergoing gynecological laparoscopic surgery: a retrospective, exploratory study.

INTRODUCTION: Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has been introduced as a novel trunk block. To date, studies comparing its clinical advantages with those of existing local anesthetic techniques are scarce. We aimed to compare the analgesic efficacy of M-TAPA to that of wound infiltration analgesia (WIA) in patients who underwent gynecological laparoscopic surgeries. METHODS: We studied medical records from January 2020 to July 2021 at Hokkaido University Hospital. The primary outcome was the number of analgesic requirements in the first 24 h postoperatively. Secondary outcomes were the time until the first analgesic requirement and adverse events regarding local anesthetic techniques. To address confounding, a regression model was used. RESULTS: Data from 90 of 231 patients were analyzed (M-TAPA group, n = 40; WIA group, n = 50). For the primary outcome, means and 95% confidence intervals for each group and between-group differences were as follows: 2.25 (1.74, 2.76), 2.28 (1.81, 2.75), and -0.03 (-0.72, 0.66), respectively. Adjusted mean difference was 0.39 (-0.32, 1.11). There were no significant differences in means between groups, with or without adjustment for covariates (p = 0.93, 0.28). Furthermore, no significant difference was detected in the time until the first analgesic requirement and adverse events related to local anesthesia. CONCLUSION: Our results demonstrate that M-TAPA did not reduce postoperative analgesic requirements compared to WIA. In a future clinical trial, sufficient visceral pain control may be required to evaluate the effectiveness of M-TAPA over WIA in patients undergoing laparoscopic gynecological surgery.

Effects of ephedrine and phenylephrine on cerebral oxygenation: observational prospective study using near-infrared time-resolved spectroscopy.

It has been reported that cerebral oxygenation (ScO2) measured by near infrared spectroscopy is maintained or increased by treatment with ephedrine, whereas almost all previous reports demonstrated that phenylephrine reduced ScO2. As the mechanism of the latter, the interference of the extracranial blood flow, that is extracranial contamination, has been suspected. Accordingly, in this prospective observational study, we utilized time-resolved spectroscopy (TRS), in which the effect of extracranial contamination is thought to be minimal, and evaluated whether the same result was obtained. We measured the changes in ScO2 as well as the total cerebral hemoglobin concentration (tHb) after treatment with ephedrine or phenylephrine during laparoscopic surgery by using a tNIRS-1 (Hamamatsu Photonics, Hamamatsu, Japan), which is a commercial instrument utilizing TRS. Based on a mixed-effects model with random intercepts for ScO2 or tHb including mean blood pressure, the mean difference and 95% confidence interval were evaluated as well as the predicted mean difference and its confidence interval using the interquartile range of mean blood pressure. Fifty treatments with ephedrine or phenylephrine were done. The mean differences of ScO2 were less than 0.1% and the predicted mean differences were less than 1.1% for the two drugs. The mean differences of tHb were less than 0.02 µM and the predicted mean differences were less than 0.2 µM for the drugs. The changes in ScO2 and tHb after treatments with ephedrine and phenylephrine were very small and clinically insignificant when measured by TRS. Previous reports about phenylephrine may have been affected by extracranial contamination.

Effect of cerebrospinal fluid drainage pressure in descending and thoracoabdominal aortic repair: a prospective multicenter observational study.

PURPOSE: Cerebrospinal fluid drainage (CSFD) is recommended during open or endovascular thoracic aortic repair. However, the incidence of CSFD complications is still high. Recently, CSF pressure has been kept high to avoid complications, but the efficacy of CSFD at higher pressures has not been confirmed. We hypothesize that CSFD at higher pressures is effective for preventing motor deficits. METHODS: This prospective observational study included 14 hospitals that are members of the Japanese Society of Cardiovascular Anesthesiologists. Patients who underwent thoracic and thoracoabdominal aortic repair were divided into four groups: Group 1, CSF pressure around 10 mmHg; Group 2, CSF pressure around 15 mmHg; Group 3, CSFD initiated when motor evoked potential amplitudes decreased; and Group 4, no CSFD. We assessed the association between the CSFD group and motor deficits using mixed-effects logistic regression with a random intercept for the institution. RESULTS: Of 1072 patients in the study, 84 patients (open surgery, 51; thoracic endovascular aortic repair, 33) had motor deficits at discharge. Groups 1 and 2 were not associated with motor deficits (Group 1, odds ratio (OR): 1.53, 95% confidence interval (95% CI): 0.71-3.29, p = 0.276; Group 2, OR: 1.73, 95% CI: 0.62-4.82) when compared with Group 4. Group 3 was significantly more prone to motor deficits than Group 4 (OR: 2.56, 95% CI: 1.27-5.17, p = 0.009). CONCLUSION: CSFD is not associated with motor deficits in thoracic and thoracoabdominal aortic repair with CSF pressure around 10 or 15 mmHg.

Change in cerebral circulation during the induction of anesthesia with remimazolam.

PURPOSE: Remimazolam is a new ultra-short-acting benzodiazepine with unknown effects on cerebral circulation. We measured total cerebral hemoglobin concentrations, which reflect cerebral blood volume (CBV), and cerebral oxygen saturation, using time-domain near-infrared spectroscopy, which can measure the absolute values of cerebral hemoglobin concentrations. We also measured cerebral blood flow velocity (CBFV) in the middle cerebral artery using transcranial Doppler as an indicator of cerebral blood flow (CBF). We did so to examine the effect of remimazolam on cerebral circulation in humans, as assessed CBV, CBF, and cerebral oxygen saturation. METHODS: This was a prospective, observational study. Fifteen patients without serious complications scheduled for general anesthesia were recruited. We measured total cerebral hemoglobin concentrations, CBFV, and cerebral oxygen saturation throughout the anesthetic induction course with remimazolam. RESULTS: Total cerebral hemoglobin concentrations did not change during the process (p = 0.51). In contrast, the mean CBFV was reduced by 11% (significant, p = 0.04). The drop in mean blood pressure following the induction of anesthesia was 17%; however, it was within the range of cerebrovascular autoregulation. Moreover, cerebral oxygen saturation increased by 4% (statistically significant, p < 0.01). CONCLUSIONS: We found that anesthetic induction with remimazolam did not alter CBV and reduced CBF in uncomplicated patients.

Changes in Cerebral Hemodynamics During Systemic Pulmonary Shunt and Pulmonary Artery Banding in Infants with Congenital Heart Disease.

Palliative surgery is often performed in the treatment of congenital heart disease. Two representative palliative procedures are the systemic pulmonary shunt and pulmonary artery banding. Dramatic changes in cerebral hemodynamics may occur in these operations due to changes in the pulmonary-to-systemic blood flow ratio and systemic oxygenation. However, there seem to be almost no studies evaluating them. Accordingly, we evaluated cerebral perfusion by transcranial Doppler ultrasonography and cerebral oxygenation by near infrared spectroscopy during these procedures. In the post hoc analysis of a previous prospective observational study, cerebral blood flow velocities of the middle cerebral artery measured by transcranial Doppler were compared between the start and end of surgery as were the pulsatility index and resistance index. The cerebral oxygenation values were also compared between the start and end of surgery. Twenty-two infants with systemic pulmonary shunt and 20 infants with pulmonary artery banding were evaluated. There were no significant differences of the flow velocities between the start and end of surgery in either procedure. The pulsatility index significantly increased after pulmonary artery banding, which may compete with the increase in cerebral perfusion due to the increase in systemic blood flow. The cerebral oxygenation decreased in both procedures, possibly due to an increase in body temperature. Arterial oxygen saturation was almost the same before and after both procedures. Contrary to our expectation, the changes in cerebral hemodynamics in the palliative operations were small if the management of physiological indices such as arterial oxygen saturation was properly performed during the procedures.

Temperature-controlled laser thermal therapy system using a newly developed laparoscopic system equipped with an ultra-compact thermographic camera.

Laser thermal therapy is one of the treatments for malignant tumors. We developed a thermal endoscope using an ultra-compact thermo-sensor and established a new laparoscopic laser thermal therapy system to heat cancer tissue at an appropriate temperature, focusing on the fact that thermographic cameras are capable of two-dimensional temperature mapping. Hepatocellular carcinoma (N1S1) cells were implanted into the livers of Sprague-Dawley rats (n = 13) to create orthotopic hepatocellular carcinoma. Six of the rats underwent laparoscopic laser thermotherapy (70 °C, 5 min) using the newly developed system, and the others underwent laparoscopic insertion only. Lesion volume measurement and histological evaluation were performed in all of the rats. The laparoscopic laser thermal therapy system provided stable temperature control. When a temperature of 70 °C was used for the set temperature, the temperature of the target cancer was maintained within the range of 68-72 °C for 93.2% of the irradiation time (5 min). The median volume of the tumors that were thermally treated was significantly smaller than that of the untreated tumors. The newly developed laparoscopic laser thermal therapy system was capable of maintaining the temperature of the tumor surface at any desired temperature and was proven to be effective in treatment of the rat hepatocellular carcinoma model.

The relationship between years of anesthesia experience and first-time intubation success rate with direct laryngoscope and video laryngoscope in infants: a retrospective observational study.

PURPOSE: Studies in adults have reported that video laryngoscope is more useful than direct laryngoscope when training less experienced anesthesiologists. However, whether this is true for infants remains unclear. Therefore, this study aimed to evaluate whether the use of video laryngoscope would result in smaller differences in success rate according to anesthesiologists' expertise than those in direct laryngoscope. METHODS: Medical records and video recordings from the operating room of patients aged < 1 year who underwent non-cardiac surgery between March 2019 and September 2021 were reviewed. Tracheal intubations between April 8, 2020, and June 20, 2021, were excluded due to the shortage of video laryngoscope blades during the COVID-19 pandemic. Rates of first-time tracheal intubation success were compared by years of anesthesia experience and initial intubation device. RESULTS: In total, 125 of 175 tracheal intubations were analyzed (direct laryngoscope group, n = 72; video laryngoscope group, n = 53). The first-time tracheal intubation success rate increased with years of experience as an anesthesiologist in the direct laryngoscope group (odds ratio OR 1.70, 95% confidence interval CI 1.15, 2.49; P = 0.0070), but not the video laryngoscope group (OR 0.99, 95% CI 0.74, 1.35; P = 0.99). CONCLUSION: The differences in success rate according to the anesthesiologists' years of experience were non-significant when using video laryngoscope in infants, compared to those in direct laryngoscope.

Age Difference of the Relationship Between Cerebral Oxygen Saturation and Physiological Parameters in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: Analysis Using the Random-Effects Model.

Recently, monitoring of cerebral oxygen saturation (ScO2) has become widespread in pediatric cardiac surgery. Our previous study reported that mean blood pressure (mBP) was the major contributor to ScO2 throughout cardiac surgery with cardiopulmonary bypass (CPB) in children weighing under 10 kg. We speculated that this result might be attributable to incomplete cerebral autoregulation in such young children. Accordingly, our hypothesis is that the relationship between ScO2 and the physiological parameters may change according to the growth of the children. ScO2 was measured with an INVOS 5100C (Somanetics, Troy, MI). Random-effects analysis was employed with ScO2 as a dependent variable, and seven physiological parameters (mBP, central venous pressure, nasopharyngeal temperature, SaO2, hematocrit, PaCO2, and pH) were entered as independent covariates. The analysis was performed during the pre-CPB, CPB, and post-CPB periods by dividing the patients into two groups: infants (Infant Group) and children who were more than 1 year old (Child Group). The Infant and Child Groups consisted of 28 and 21 patients. In the random-effects analysis, mBP was the major contributor to ScO2 during CPB in both groups. During the pre-CPB period, the effect of mBP was strongest in the Infant group. However, its effect was second to that of SaO2 in the Child Group. During the post-CPB period, SaO2 and mBP still affected ScO2 in the Infant group. However, the dominant contributors were unclear in the Child Group. Cerebral autoregulation may be immature in infants. In addition, it may be impaired during CPB even after 1 year of age.

Intraoperative myocardial infarction and refractory cardiogenic shock during major hepatectomy: a case report.

BACKGROUND: Myocardial infarction (MI) complicated by cardiogenic shock during non-cardiac surgery is a rare but fatal complication. The management of intraoperative MI is challenging. CASE PRESENTATION: A 77-year-old hypertensive man with good functional capacity was scheduled for hepatectomy. After the start of liver resection, the electrocardiogram monitor showed ST depression, and the patient developed refractory cardiogenic shock. Transesophageal echocardiography revealed severe hypokinesis of the anteroseptal wall. The surgery was suspended, and an intra-aortic balloon pump was placed following immediate abdominal closure. Coronary angiography revealed severe stenosis of the left main coronary trunk, and percutaneous coronary intervention (PCI) was performed. Myocardial wall motion improved, and blood pressure stabilized. Two days after PCI, hepatectomy, which had been suspended, was successfully completed. CONCLUSIONS: Once intraoperative MI has occurred, early diagnosis and multidisciplinary approaches are important to manage the difficult clinical situation.

Measuring Task-Related Brain Activity With Event-Related Potentials in Dynamic Task Scenario With Immersive Virtual Reality Environment.

Measurement of event-related potentials (ERPs) in simulated and real environments is advantageous for understanding cognition and behavior during practice of goal-directed activities. Recently, instead of using task-irrelevant "probe stimuli" to elicit ERPs, extraction of ERPs directly from events that occur in simulated and real environments has drawn increased attention. Among the previous ERP studies using immersive virtual reality, only a few cases elicited ERPs from task-related events in dynamic task settings. Furthermore, as far as we surveyed, there were no studies that examined the source of ERPs or correlation between ERPs and behavioral performance in 360-degree immersive virtual reality using head-mounted display. In this study, EEG signals were recorded from 16 participants while they were playing the first-person shooter game with immersive virtual reality environment. Error related negativity (ERN) and correct-(response)-related negativity (CRN) elicited by shooting-related events were successfully extracted. We found the ERN amplitudes to be correlated with the individual shooting performance. Interestingly, the main source of the ERN was the rostral anterior cingulate cortex (ACC), which is different from previous studies where the signal source was often estimated to be the more caudal part of ACC. The obtained results are expected to contribute to the evaluation of cognitive functions and behavioral performance by ERPs in a simulated environment.

H12-(ADP)-liposomes for hemorrhagic shock in thrombocytopenia: Mesenteric artery injury model in rabbits.

BACKGROUND: Damage control resuscitation improves patient outcomes after severe hemorrhage and coagulopathy. However, effective hemostasis methods for these critical situations are lacking. OBJECTIVE: We evaluated the hemostatic efficacy of fibrinogen γ-chain (HHLGGAKQAGDV, H12)-coated, adenosine-diphosphate (ADP)-encapsulated liposomes (H12-[ADP]-liposomes) in thrombocytopenic rabbits with hemorrhagic shock. METHODS: Acute thrombocytopenia (80%) was induced in rabbits that also received mesenteric vessel injury, leading to hemorrhagic shock. Five minutes after injury, subjects received intravenous bolus injection with H12-(ADP)-liposomes (20 mg/kg), followed by isovolemic transfusion with stored red blood cells (RBCs)/platelet poor plasma (PPP) (RBC:PPP = 1:1 [vol/vol]), or lactated Ringer solution every 5 min to compensate blood loss. One group received H12-(phosphate buffered saline [PBS]) liposomes followed by RBC/PPP. Additional groups were received isovolemic transfusion with RBC/platelet rich plasma (PRP) (RBC:PRP = 1:1 [vol/vol]), RBC/PPP, PPP alone, or lactated Ringer solution. RESULTS: Treatment with H12-(ADP)-liposomes followed by RBC/PPP transfusion and RBC/PRP transfusion effectively stopped bleeding in all thrombocytopenic rabbits. In contrast, three of 10 rabbits treated with RBC/PPP failed hemostasis, and no rabbits receiving lactated Ringer solution stopped bleeding or survived. Twenty-four hours after hemorrhage, 80% of rabbits receiving H12-(ADP)-liposome followed by RBC/PPP transfusion survived and 70% of rabbits receiving RBC/PRP transfusion also survived, although RBC/PPP-transfused rabbits showed 40% survival. Rabbits receiving H12-(ADP)-liposomes followed by lactated Ringer solution showed a transient hemostatic potential but failed to survive. H12-(PBS)-liposomes showed no beneficial effect on hemostasis. Neither the PPP group nor the lactated Ringer group survived. CONCLUSION: H12-(ADP)-liposome treatment followed by RBC/PPP may be effective in lethal hemorrhage after mesenteric vessel injury in coagulopathic rabbits.

Neonatal isoflurane exposure disturbs granule cell migration in the rat dentate gyrus.

It has been reported that neonatal isoflurane exposure causes behavioral abnormalities following neurodegeneration in animals and gamma-aminobutyric acid type A (GABAA) receptor activation during the synaptogenesis is considered to be one possible trigger. Additionally, the inhibitory effect of excitatory GABAA receptor signaling on the granule cell (GC) migration in the neonatal rat dentate gyrus (DG) was reported in a febrile seizure model. Then, we hypothesized that neonatal isoflurane exposure, which activates GABAA receptor, causes GC migration disturbances in the neonatal rat. Rat pups were injected with 5-bromo-2'-deoxyuridine (BrdU) and divided into five treatment groups, and double immunofluorescent staining targeting BrdU and homeobox prospero-like protein 1 (Prox1) was performed to examine the localization of BrdU/Prox1 colabeled cells, and then the GC migration was assessed. As a result, we found that the ectopic migration of GC after 2% isoflurane exposure on postnatal day 7 significantly increased after P21. The number of hilar ectopic GCs was influenced by the concentration of isoflurane and the exposure day but not by carbon dioxide exposure. Our main finding is that neonatal isoflurane anesthesia disturbs the migration of GCs in the rat DG, which may be one possible mechanism underlying the neurotoxicity following neonatal isoflurane anesthesia.

Effects of the Prone Position on Regional Neutrophilic Lung Inflammation According to 18F-FDG Pet in an Experimental Ventilator-Induced Lung Injury Model.

ABSTRACT: Ventilator-induced lung injury (VILI) can be life-threatening and it is important to prevent the development of VILI. It remains unclear whether the prone position affects neutrophilic inflammation in the lung regions in vivo, which plays a crucial role in the pathogenesis of VILI. This study aimed to assess the relationship between the use of the prone position and the development of VILI-associated regional neutrophilic lung inflammation. Regional neutrophilic lung inflammation and lung aeration during low tidal volume mechanical ventilation were assessed using in vivo 2-deoxy-2-[(18)F] fluoro-D-glucose (18F-FDG) positron emission tomography and computed tomography in acutely experimentally injured rabbit lungs (lung injury induced by lung lavage and excessive ventilation). Direct comparisons were made among three groups: control, supine, and prone positions. After approximately 7 h, tissue-normalized 18F-FDG uptake differed significantly between the supine and prone positions (SUP: 0.038 ±â€Š0.014 vs. PP: 0.029 ±â€Š0.008, P = 0.038), especially in the ventral region (SUP: 0.052 ±â€Š0.013 vs. PP: 0.026 ±â€Š0.007, P = 0.003). The use of the prone position reduced lung inhomogeneities, which was demonstrated by the correction of the disproportionate rate of voxel gas over the given lung region. The progression of neutrophilic inflammation was affected by the interaction between the total strain (for aeration) and the inhomogeneity. The prone position is effective in slowing down the progression of VILI-associated neutrophilic inflammation. Under low-tidal-volume ventilation, the main drivers of its effect may be homogenization of lung tissue and that of mechanical forces.