Prazosin Potentiates Mast Cell-Stabilizing Property of Adrenaline.

BACKGROUND/AIMS: Adrenaline quickly inhibits the release of histamine from mast cells. Besides ß2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties. METHODS: Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists. RESULTS: Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a ß2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells. CONCLUSION: This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell-stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by ß2-adrenergic receptors.

Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity.

BACKGROUND: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman's test was used for correlation analysis. Statistical significance was set at P < .05. RESULTS: TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/µL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/µL), with an average treatment effect of 98/µL (95% confidence interval [CI], 2-270/µL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/µL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/µL), with an average treatment effect (ATE) of 79/µL (95% CI, 19-171/µL); these EDEV levels remained elevated until day 5. CONCLUSIONS: EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

Impact of intraoperative fluid management on postoperative complications in patients undergoing minimally invasive esophagectomy for esophageal cancer: a retrospective single-center study.

BACKGROUND: Esophagectomy is a high-risk procedure that can involve serious postoperative complications. There has been an increase in the number of minimally invasive esophagectomies (MIEs) being performed. However, the relationship between intraoperative management and postoperative complications in MIE remains unclear. METHODS: After the institutional review board approval, we enrolled 300 patients who underwent MIE at Tohoku University Hospital between April 2016 and March 2021. The relationships among patient characteristics, intraoperative and perioperative factors, and postoperative complications were retrospectively analyzed. The primary outcome was the relationship between intraoperative fluid volume and anastomotic leakage, and the secondary outcomes included the associations between other perioperative factors and postoperative complications. RESULTS: Among 300 patients, 28 were excluded because of missing data; accordingly, 272 patients were included in the final analysis. The median [interquartile range] operative duration was 599 [545-682] minutes; total intraoperative infusion volume was 3,747 [3,038-4,399] mL; total infusion volume per body weight per hour was 5.48 [4.42-6.73] mL/kg/h; and fluid balance was + 2,648 [2,015-3,263] mL. The postoperative complications included anastomotic leakage in 68 (25%) patients, recurrent nerve palsy in 91 (33%) patients, pneumonia in 62 (23%) patients, cardiac arrhythmia in 13 (5%) patients, acute kidney injury in 5 (2%) patients, and heart failure in 5 (2%) patients. The Cochrane-Armitage trend test indicated significantly increased anastomotic leakage among patients with a relatively high total infusion volume (P = 0.0085). Moreover, anastomotic leakage was associated with male sex but not with peak serum lactate levels. Patients with a longer anesthesia duration or recurrent nerve palsy had a significantly higher incidence of postoperative pneumonia than those without. Further, the incidence of postoperative pneumonia was not associated with the operative duration, total infusion volume, or fluid balance. The operative duration and blood loss were related to the total infusion volume. Acute kidney injury was not associated with the total infusion volume or serum lactate levels. CONCLUSIONS: Among patients who underwent MIE, the total infusion volume was positively correlated with the incidence of anastomotic leakage. Further, postoperative pneumonia was associated with recurrent nerve palsy but not total infusion volume or fluid balance.

Accuracy of Cardiac Output Measured by Fourth-Generation FloTrac and LiDCOrapid, and Their Characteristics Regarding Systemic Vascular Resistance in Patients Undergoing Cardiac Surgery.

OBJECTIVES: The clinical use of less-invasive devices that calculate the cardiac output from arterial pressure waveform is increasing. The authors aimed to evaluate the accuracy and characteristics of the systemic vascular resistance index (SVRI) of the cardiac index measured by 2 less-invasive devices, fourth-generation FloTrac (CIFT) and LiDCOrapid (CILR), compared with the intermittent thermodilution technique, using a pulmonary artery catheter (CITD). DESIGN: This was a prospective observational study. SETTING: This study was conducted at a single university hospital. PARTICIPANTS: Twenty-nine adult patients undergoing elective cardiac surgery. INTERVENTIONS: Elective cardiac surgery was used as an intervention. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, CIFT, CILR, and CITD, were measured after the induction of general anesthesia, at the start of cardiopulmonary bypass, after completion of weaning from cardiopulmonary bypass, 30 minutes after weaning, and at sternal closure (135 measurements in total). The CIFT and CILR had moderate correlations with CITD (r = 0.62 and 0.58, respectively). Compared with CITD, CIFT, and CILR had a bias of -0.73 and -0.61 L/min/m2, limit of agreement of -2.14-to-0.68 L/min/m2 and -2.42-to-1.20 L/min/m2, and percentage error of 39.9% and 51.2%, respectively. Subgroup analysis for evaluating SVRI characteristics showed that the percentage errors of CIFT and CILR were 33.9% and 54.5% in low SVRI (<1,200 dyne×s/cm5/m), 37.6% and 47.9% in moderate SVRI (1,200-1,800 dyne×s/cm5/m), 49.3% and 50.6% in high SVRI (>1,800 dyne·s/cm5/m2), respectively. CONCLUSIONS: The accuracy of CIFT or CILR was not clinically acceptable for cardiac surgery. Fourth-generation FloTrac was unreliable in high SVRI. LiDCOrapid was inaccurate across a broad range of SVRI, and minimally affected by SVRI.

Postreperfusion Syndrome Presenting as Posttransplant Portal Hypertension due to Prolonged Elevation of Pulmonary Vascular Resistance and the Role of Nitroglycerin in Diagnosis and Treatment: A Case Report of Budd-Chiari Syndrome.

Postreperfusion syndrome is one of the responsible mechanisms of portal hypertension in patients undergoing liver transplantation. And post-transplant portal hypertension causes graft dysfunction. Postreperfusion syndrome is characterized by a decrease in arterial pressure and cardiac output, and an increase in central venous pressure, pulmonary artery pressure, and pulmonary vascular resistance that occurs after the release of the portal vein clamp. Although early recovery from postreperfusion syndrome is desired, there is a little medication therapy such as the administration of calcium chloride, sodium bicarbonate, and beta-agonist for postreperfusion syndrome. We present a case of postreperfusion syndrome manifested as post-transplant portal hypertension and reversed after nitroglycerin administration. A 49-year-old Asian woman was scheduled for liver transplantation because of Budd-Chiari syndrome. After portal vein reperfusion, she experienced severe postreperfusion syndrome. Administration of ephedrine and calcium restored arterial pressure; however, pulmonary artery pressure, pulmonary vascular resistance, and central venous pressure elevations were sustained, causing right ventricular overload. This condition did not improve after hepatic artery reperfusion, and caused post-transplant portal hypertension. After nitroglycerin administration, pulmonary vascular resistance and central venous pressure decreased, mean arterial pressure increased, right heart contractility recovered, and portal hypertension disappeared. Hemodynamic improvement by nitroglycerin administration helped in diagnosing postreperfusion syndrome and avoiding unnecessary splenectomy. If portal vein pressure increases after liver transplantation, the change in hemodynamic parameters by nitroglycerin administration should be assessed, which will lead to accurate diagnosis and appropriate treatment. Furthermore, postreperfusion syndrome should be listed as a differential diagnosis of post-transplant portal hypertension.

Effectiveness of substantial shortening of the endotracheal tube for decreasing airway resistance and increasing tidal volume during pressure-controlled ventilation in pediatric patients: a prospective observational study.

The endotracheal tubes (ETTs) used for children have a smaller inner diameter. Accordingly, the resistance across ETT (RETT) is higher. Theoretically, shortening the ETTs can decrease total airway resistance (Rtotal), because Rtotal is sum of RETT and patient's airway resistance. However, the effectiveness of ETT shortening for mechanical ventilation in the clinical setting has not been reported. We assessed the effectiveness of shortening a cuffed ETT for decreasing Rtotal, and increasing tidal volume (TV), and estimated the RETT/Rtotal ratio in children. In anesthetized children in a constant pressure-controlled ventilation setting, Rtotal and TV were measured with a pneumotachometer before and after shortening a cuffed ETT. In a laboratory experiment, the pressure gradient across the original length, shortened length, and the slip joint alone of the ETT were measured. We then determined the RETT/Rtotal ratio using the above results. The clinical study included 22 children. The median ETT percent shortening was 21.7%. Median Rtotal was decreased from 26 to 24 cmH2O/L/s, and median TV was increased by 6% after ETT shortening. The laboratory experiment showed that ETT length and the pressure gradient across ETT are linearly related under a certain flow rate, and approximately 40% of the pressure gradient across the ETT at its original length was generated by the slip joint. Median RETT/Rtotal ratio were calculated as 0.69. The effectiveness of ETT shortening on Rtotal and TV was very limited, because the resistance of the slip joint was very large.

Worsening Right Ventricular Function during Cardiac Surgery Is a Strong Predictor of Postoperative Acute Kidney Injury: A Prospective Observational Study.

This prospective, observational study was conducted in a university hospital to verify that intraoperative worsening of right ventricular function causes cardiac surgery-associated acute kidney injury. Adult patients undergoing cardiac surgery under mid-sternal incision with cardiopulmonary bypass were included. Echocardiographic right and left ventricular function parameters were measured before and after bypass and compared using the Wilcoxon signed-rank test. Perioperative serum creatinine values at baseline and within the first 48 hours postoperatively were measured for the diagnosis of acute kidney injury. Spearman rank-order correlation (ρ) and receiver operating characteristic analysis were used to reveal relationships. Thirty-four patients were evaluated. Right ventricular ejection fraction (56.2 ± 7.0 vs. 51.6 ± 7.2%; P = 0.0002), right ventricular fractional area change (49.1 ± 6.4 vs. 46.6 ± 5.3%; P = 0.0201; mean ± standard deviation), and left ventricular ejection fraction (57.4 ± 6.1 vs. 51.7 ± 6.2%; P < 0.0001) were significantly decreased. Central venous pressure was significantly increased (7.2 ± 3.5 vs. 9.7 ± 3.7; P = 0.0001). Serum creatinine values increased from 0.82 [0.70-1.08] to 0.99 [0.82-1.54] mg/dL (P < 0.0001; median [interquartile range]). Changes in right ventricular ejection fraction, fractional area change, and right ventricular strain during cardiovascular surgery were significantly correlated with changes in serum creatinine values. Fractional area change exhibited the strongest correlation (ρ = -0.61, P < 0.0001). Change in fractional area change showed an area under the curve of 0.902 and a cutoff value of -2.1, which predicted acute kidney injury with 92% sensitivity, 73% specificity, and 79% accuracy. The functions of both ventricles were decreased after cardiopulmonary bypass. Worsening right ventricular function was independently correlated with postoperative renal dysfunction, and fractional area change was the strongest predictor of cardiac surgery-associated acute kidney injury.

Influence of Respiratory Gas Density on Tidal Volume during Mechanical Ventilation: A Laboratory Investigation and Observational Study in Children.

Fluid mechanics show that high-density gases need more energy while flowing through a tube. Thus, high-density anesthetic gases consume more energy to flow and less energy for lung inflation during general anesthesia. However, its impact has not been studied. Therefore, this study aimed to investigate the effects of high-density anesthetic gases on tidal volume in laboratory and clinical settings. In the laboratory study, a test lung was ventilated at the same pressure-controlled ventilation with 22 different gas compositions (density range, 1.22-2.27 kg/m3) using an anesthesia machine. A pneumotachometer was used to record the tidal volume of the test lung and the respiratory gas composition; it showed that the tidal volume of the test lung decreased as the respiratory gas density increased. In the clinical study, the change in tidal volume per body weight, accompanied by gas composition change (2% sevoflurane in oxygen and with 0-30-60% of N2O), was recorded in 30 pediatric patients. The median tidal volume per body weight decreased by 10% when the respiratory gas density increased from 1.41 kg/m3 to 1.70 kg/m3, indicating a significant between-group difference (P < 0.0001). In both settings, an increase in respiratory gas density decreased the tidal volume during pressure-controlled ventilation, which could be explained by the fluid dynamics theory. This study clarified the detailed mechanism of high-density anesthetic gas reduced the tidal volume during mechanical ventilation and revealed that this phenomenon occurs during pediatric anesthesia, which facilitates further understanding of the mechanics of ventilation during anesthesia practice and respiratory physiology.

Effects of oxytocin on responses to nociceptive and non-nociceptive stimulation in the upper central nervous system.

Oxytocin is known as a social bonding hormone, but it also functions as an anxiolytic or analgesic neurotransmitter. When oxytocin regulates pain or anxiousness centrally as a neurotransmitter, it is secreted by neurons and directly projected to targeted regions. Although the function of oxytocin at the spinal level is well studied, its effects at the supraspinal level are poorly understood. We aimed to investigate the effect of oxytocin at the supraspinal level in vivo using C57BL/6J (wild-type [WT]), oxytocin-deficient (Oxt-/-), oxytocin receptor-deficient (Oxtr-/-), and oxytocin receptor-Venus (OxtrVenus/+) mice lines. Response thresholds in Oxtr-/- mice in Hargreaves and von-Frey tests were significantly lower than those in WT mice, whereas open field and light/dark tests showed no significant differences. Moreover, response thresholds in Oxt-/- mice were raised to those in WT mice after oxytocin administration. Following the Hargreaves test, we observed the co-localisation of c-fos with Venus or the oxytocin receptor in the periaqueductal gray (PAG), medial amygdala (MeA), and nucleus accumbens (NAc) regions in OxtrVenus/+ mice. Furthermore, in the PAG, MeA, and NAc regions, the co-localisation of oxytocin with c-fos and gamma-aminobutyric acid was much stronger in Oxtr-/- mice than in WT mice. However, following von-Frey test, the same findings were observed only in the MeA and NAc regions. Our results suggest that oxytocin exerts its analgesic effect on painful stimulation via the PAG region and a self-protective effect on unpleasant stimulation via the MeA and NAc regions.

A clinical study comparing ultrasound-measured pyloric antrum cross-sectional area to computed tomography-measured gastric content volume to detect high-risk stomach in supine patients undergoing emergency abdominal surgery.

The main aim of this study was to assess whether the ultrasound examination and measurement of the pyloric antral cross-sectional area (antral-CSA) in the supine position could be useful to diagnose a full stomach using a computed tomography (CT) as a comparator in emergency patients. Immediately before general anesthesia induction in patients undergoing emergency abdominal surgery, antral-CSA was measured and the volume of the gastric contents was evaluated via ultrasound in the supine position. Gastric content volume was also calculated from a CT image taken prior to the operation. The primary outcome of this study was to determine the antral-CSA threshold of the "high-risk stomach" defined as the presence of solid/thick fluid and/or gastric content volume > 1.5 mL/kg. The secondary outcome was to evaluate the correlation between gastric content volume calculated by CT and antral-CSA. Thirty-nine patients provided consent and were included. Ten patients had gastric contents over 1.5 mL/kg, and 18 patients showed solid contents/thick fluids. The median [IQR] antral-CSA and gastric content volume were 3.82 [2.74-5.07] cm2 and 0.32 [0.09-2.08] mL/kg, respectively. The antral-CSA cutoff value of "high-risk stomach" was 3.01 cm2. This value had a sensitivity of 85%, a negative predictive value of 53%, and AUC of the ROC of 0.670 (p = 0.03). The Spearman rank-order correlation between both measures was 0.420 (p = 0.01). The correlation was improved, particularly in stomachs with solid contents/thick fluids. Antral-CSA measured in the supine position may help to assess the high-risk stomach patients undergoing emergency surgery.Trial registration: www.umin.ac.jp (UMIN 000013416). Registered 14 March 2014.

Increase in circulating ACE-positive endothelial microparticles during acute lung injury.

Circulating endothelial microparticles (EMPs) are considered to be markers of endothelial injury, and lung microvascular endothelial cells express higher levels of angiotensin-converting enzyme (ACE). The aim of this study is to examine whether the number of ACE+ microvascular EMPs could be a prognostic marker for the development of acute respiratory distress syndrome (ARDS) in septic patients.The numbers of EMPs and ACE+ EMPs in the culture supernatant from human microvascular endothelial cells, as well as in the blood of mouse lung injury models and septic patients (n=82), were examined using flow cytometry.ACE+ EMPs in the culture supernatant from pulmonary microvascular endothelial cells increased after exposure to an inflammatory stimulus. In the mouse lung injury models, the circulating ACE+ EMPs and ACE+ EMP/EMP ratio were higher than in the controls (p<0.001). The ACE+ EMP/EMP ratio was correlated with the wet/dry lung ratio (rs=0.775, p<0.001). The circulating ACE+ EMPs and ACE+ EMP/EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001).Therefore, circulating ACE+ EMPs may be a prognostic marker for the development of ARDS in the septic patients.

Influences of environmental noise level and respiration rate on the accuracy of acoustic respiration rate monitoring.

We tested the hypothesis that the environmental noise generated by a forced-air warming system reduces the monitoring accuracy of acoustic respiration rate (RRa). Noise levels were adjusted to 45-55, 56-65, 66-75, and 76-85 dB. Healthy participants breathed at set respiration rates (RRset) of 6, 12, and 30/min. Under each noise level at each RRset, the respiration rates by manual counting (RRm) and RRa were recorded. Any appearance of the alarm display on the RRa monitor was also recorded. Each RRm of all participants agreed with each RRset at each noise level. At 45-55 dB noise, the RRa of 13, 17, and 17 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of 14, 17, and 16 participants at 56-65 dB noise, agreed with RRset of 6, 12, and 30/min, respectively. At 66-75 dB noise, the RRa of 9, 15, and 16 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of one, nine, and nine participants at 76-85 dB noise agreed with RRset of 6, 12, and 30/min, respectively, which was significantly less than the other noise levels (P < 0.05). Overall, 72.9% of alarm displays highlighted incorrect values of RRa. In a noisy situation involving the operation of a forced-air warming system, the acoustic respiration monitoring should be used carefully especially in patients with a low respiration rate.

Impact of Pain on Incident Risk of Disability in Elderly Japanese: Cause-specific Analysis.

BACKGROUND: Although several cross-sectional studies have reported that pain is associated with functional disability in the elderly, data regarding a longitudinal association between pain and disability are inconsistent. This study aimed to investigate the association of pain severity with subsequent functional disability due to all causes as well as stroke, dementia, and joint disease/fracture. METHODS: The authors conducted a prospective cohort study of 13,702 Japanese individuals aged 65 yr or older. Information regarding pain severity during the previous 4 weeks and other lifestyle factors was collected via questionnaire in 2006. Data on the incidence of functional disability were retrieved from the Long-term Care Insurance database. Cox proportional hazards regression analysis was used to estimate the multivariate-adjusted hazard ratios for incident functional disability. RESULTS: The authors documented 2,686 (19.6%) cases of incident functional disability. The multivariate hazard ratio of functional disability was 1.15 (95% CI, 1.02 to 1.31) among respondents with moderate pain and 1.31 (95% CI, 1.12 to 1.54) among respondents with severe pain in comparison with those without pain (P trend < 0.001). These positive associations were particularly remarkable for disability due to joint disease/fracture: the multivariate hazard ratio was 1.88 (95% CI, 1.37 to 2.58) for moderate pain and 2.76 (95% CI, 1.93 to 3.95) for severe pain (P trend < 0.001). There was a negative association between pain severity and disability due to dementia (P trend = 0.041) and no significant association between pain severity and disability due to stroke. CONCLUSIONS: Among elderly Japanese individuals, the authors found a significant positive association between pain severity and future incident functional disability.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

AIM: Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. METHODS: Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. RESULTS: The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. CONCLUSIONS: This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF.

Positive pressure ventilation in a patient with a right upper lobar bronchocutaneous fistula: right upper bronchus occlusion using the cuff of a left-sided double lumen endobronchial tube.

In patients with a bronchocutaneous fistula, positive pressure ventilation leads to air leakage and potential hypoxemia. A male patient with a right upper bronchocutaneous fistula was scheduled for esophageal reconstruction. His preoperative chest computed tomography image revealed aeration in the right middle and lower lobe, a large bulla in the left upper lobe, and pleural effusion and pneumonia in the left lower lobe. Therefore, left one-lung ventilation was considered to result in hypoxemia. Before anesthesia induction, the bronchocutaneous fistula was covered with gauze and film to prevent air leakage. After anesthesia induction, mask ventilation was performed with a peak positive pressure of 10 cmH2O. A left-sided double lumen endobronchial tube (DLT) was then inserted into the right main bronchus for occluding only the right superior bronchus, and two-lung ventilation was performed to minimize airway pressure and maintain oxygenation, which did not cause air leakage through the fistula. During anesthesia, no ventilation-related difficulty was faced. The method of inserting a left-sided DLT into the right main bronchus and occluding the right upper bronchus selectively by bronchial cuff is considered to be an option for mechanical ventilation in patients with a right upper bronchial fistula, as demonstrated in the present case.

The impact of liver disorders on perioperative management of reoperative cardiac surgery: a retrospective study in adult congenital heart disease patients.

PURPOSE: We evaluated the preoperative prevalence of risk factors for liver disorders and the relationship between the liver disorders and perioperative outcomes in adult congenital heart disease (ACHD) patients. METHODS: This retrospective study included 32 ACHD patients who underwent reoperative cardiac surgery. RESULTS: Preoperatively, 38% of the study patients had risk factors, including congestive liver (CL) due to right heart failure (31%), chronic hepatitis C (HC) (22%), and both CL and HC (16%). The numbers of patients with Child-Pugh scores 5, 6, 7 and 8 were 22, 7, 2 and 1. Median (range) preoperative platelet count and fibrinogen values were 155 (61-330) × 103/µl and 250 (145-367) mg/dl, respectively. The patients with higher Child-Pugh scores tended to have longer duration of anesthesia and surgery (p = 0.078, 0.078, respectively), and had significantly higher platelet transfusion (p = 0.031). Lower platelet count was associated with longer duration of anesthesia, surgery and cardio pulmonary bypass (CPB), and larger amount of blood loss and platelet transfusion (p = 0.01, 0.011, 0.024, 0.033, 0.021). Lower fibrinogen value was associated with longer duration of anesthesia, surgery and CPB, and larger amount of platelet transfusion (p = 0.015, 0.009, 0.009, 0.023). CONCLUSION: ACHD patients who underwent reoperative cardiac surgery had a high prevalence of risk factors for liver disorders preoperatively, and liver disorders aggravated some intraoperative outcomes. These findings suggest that the prevention of liver disorders is important for reducing the occurrence of poor outcomes, and that ACHD patients with liver disorders need attentive perioperative management.

[Six Cases of Anesthetic Management of Adult Patients Undergoing Coarctation of Aorta Repair].

BACKGROUND: In Japan, every year more than 9,000 patients with congenital heart disease reach adulthood due to improved medical treatments. Adult coarctation of aorta (CoA) patient is likely to need surgery for re- CoA, progressive CoA and/or aortic aneurysm. There- fore, it is necessary to consider anesthetic management of complicated aortic surgery of CoA patient Methods: This is a retrospective study of six pa- tients with CoA who underwent the CoA repair sur- gery in adulthood from 2005 to 2013. RESULTS: Pre-operative CoA diameter was 7.8?2.5 mm and pressure gradient was 37±13 mmHg. Four patients had aortic aneurysm. Three patients received lateral thoracotomy and one-lung ventilation; five patients underwent selective cerebral perfusion. As perioperative complications, all two patients with re-CoA surgery had pneumothorax; two of five patients with arch repair surgery had recurrent nerve paralysis; a patient with left subclavian artery ischemia/reperfu- sion, and elevation and flexion of left upper extremity position had left upper extremity paralysis. CONCLUSIONS: In anesthetic management of adult CoA repair, it is important to understand various surgical approach and corresponding ventilation and extracorporeal circulation methods and possible complications.

Chlorpromazine-induced changes in membrane micro-architecture inhibit thrombopoiesis in rat megakaryocytes.

Chlorpromazine often causes severe and persistent thrombocytopenia. Several clinical studies have suggested the presence of an as-yet-unknown mechanism in this drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. As we previously demonstrated in rat peritoneal mast cells or adipocytes, chlorpromazine is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane. Therefore, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of chlorpromazine on the membrane capacitance and Kv1.3-channel currents in rat megakaryocytes. By electron microscopic imaging of the cellular surface, we also examined the effects of chlorpromazine on the membrane micro-architecture of megakaryocytes. Chlorpromazine markedly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging techniques. As shown by electron microscopy, chlorpromazine actually changed the membrane micro-architecture of megakaryocytes, and was likely to halt the process of pro-platelet formation in the cells. This drug persistently decreased the membrane capacitance and almost totally and irreversibly inhibited the Kv1.3-channel currents in megakaryocytes. This study demonstrated for the first time that chlorpromazine is likely to inhibit the process of thrombopoiesis persistently in megakaryocytes, as detected by the long-lasting decrease in the membrane capacitance and the irreversible suppression of the Kv1.3-channel currents. Chlorpromazine-induced changes in the membrane micro-architecture are thought to be responsible for its persistent effects.

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties.

BACKGROUND: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm), the absence of such changes by these drugs indicates their mast cell-stabilizing properties. METHODS: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. RESULTS: Relatively lower concentrations of tranilast (100, 250 µM) and ketotifen (1, 10 µM) did not significantly affect the GTP-x03B3;-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM) and ketotifen (50, 100 µM) almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. CONCLUSIONS: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.