Prone Position Impairs Oxygen Supply-Demand Balance During Systemic Hypoxia in Rabbits

Ventilation in the prone position improves the prognosis of patients with severe acute respiratory distress syndrome (ARDS). Contraindications to ventilation in this position include unstable systemic circulation. Only a few reports exist on the effects of prone ventilation in respiratory failure on systemic circulation. This animal study compared systemic hemodynamic changes between supine and prone positions in anesthetized rabbits under acute systemic hypoxia (breathing 15% O2). Cardiac output and the systemic O2 extraction ratio increased under the hypoxia, but only in the supine group. Besides, the rate pressure product was higher in the prone group than in the supine group. This study showed that prone ventilation increases myocardial O2 consumption and suppresses compensatory mechanisms to maintain aerobic metabolism during systemic hypoxia. First of all, it will be necessary to examine the effect of prone ventilation on the O2 supply-demand balance in the ARDS model

Marathoners’ Breathing Pattern Protects Against Lung Injury by Mechanical Ventilation: An Ex Vivo Study Using Rabbit Lungs

[Background] Breathing during a marathon is often empirically conducted in a so-called “2:2 breathing rhythm,” which is based on a four-phase cycle, consisting of the 1st and 2nd inspiratory and the 1st and 2nd expiratory phases. We developed a prototype ventilator that can perform intermittent positive pressure ventilation, mimicking the breathing cycle of the 2:2 breathing rhythm. This mode of ventilation was named the marathoners’ breathing rhythm ventilation (MBV). We hypothesized that MBV may have a lung protective effect. [Methods] We examined the effects of the MBV on the pulmonary pre-edema model in isolated perfused rabbit lungs. The pulmonary pre-edema state was induced using bloodless perfusate with low colloid osmotic pressure. The 14 isolated rabbit lung preparations were randomly divided into the conventional mechanical ventilation (CMV) group and MBV group, (both had an inspiratory/expiratory ratio of 1/1). In the CMV group, seven rabbit lungs were ventilated using the Harvard Ventilator 683 with a tidal volume (TV) of 8 mL/kg, a respiratory rate (RR) of 30 cycles/min, and a positive end-expiratory pressure (PEEP) of 2 cmH2O for 60 min. In the MBV group, seven rabbit lungs were ventilated using the prototype ventilator with a TV of 6 mL/kg, an RR of 30 cycles/min, and a PEEP of 4 cmH2O (first step) and 2 cmH2O (second step) for 60 min. The time allocation of the MBV for one cycle was 0.3 s for each of the 1st and 2nd inspiratory and expiratory phases with 0.2 s of intermittent resting between each phase. [Results] Peak airway pressure and lung wet-to-dry ratio after 60 min of ventilation were lower in the MBV group than in the CMV group. [Conclusion] MBV was considered to have a lung-protective effect compared to CMV

Racemic Ketamine and S(+)-Ketamine Concentrations in Cerebrospinal Fluid after Epidural and Intravenous Administration in Rabbits

The pharmacokinetic characteristic of ketamine, particularly the shift from the epidural space to the cerebrospinal fluid (CSF), is still unclear. Furthermore pharmacokinetic differences between racemic ketamine and S(+)-ketamine are not clearly described when administered into the epidural space. We measured plasma and CSF concentrations of racemic ketamine and S(+)-ketamine after 2 mg/kg intravenous or 2 mg/kg epidural injection in 32 rabbits, and calculated pharmacokinetic parameters by the moment analysis method. The elimination half time of S(+)-ketamine was significantly shorter than that of racemic ketamine and the systemic distribution volume of S(+)-ketamine was significantly smaller than that of racemic ketamine in the CSF. Pharmacokinetic parameters in the CSF after epidural injection of racemic versus S(+)-ketamines were: maximum concentration, 0.4 ± 0.1 versus 0.6 ± 0.2 ?g/mL (not significant); time to maximum concentration, 9.7 ± 2.1 versus 9.0 ± 3.4 min (not significant); elimination half time, 127.1 ± 25.2 versus 89.3 ± 19.4 min (P = 0.005); area under the curve, 56.4 ± 6.4 versus 56.6 ± 11.0 ?g?mL/min (not significant); and distribution volume, 19,463.5 ± 3266.1 versus 13,613.3 ± 4895.2 mL (P = 0.014), respectively. When injected intravenously, there was no significant difference in these parameters of the CSF between racemic and S(+)-ketamines. Racemic ketamine passed easily through the blood brain barrier when administered intravenously. It also shifted to the CSF through the systemic circulation, even when they were administered epidurally. S(+)-Ketamine had similar movement as racemic ketamine

Evaluation of Exhaled Nitric Oxide in Thoracic Surgery Patients under One Lung Ventilation Using a Newly Designed Online Exhaled Nitric Oxide Measuring System

Measurement of exhaled nitric oxide (NO) has been gaining much interest lately. However, an ideal measuring system is not yet available in the clinical setting. The aims of the present study were to construct an exhaled NO measuring system and to investigate the effects of one lung ventilation (OLV) on exhaled NO output in patients who underwent thoracic surgery. At first, the NO measuring system was constructed with an NO analyzer, a respiratory flowmeter and a data processing computer system in which the algorithm was indwelled for correcting the distorted NO output wave form. Then, accuracy of this system was tested by using a simulator. This simulator was reworked in order to simulate NO production from the lung under both spontaneous respiration and mechanical ventilation. The data of peak NO concentration (pNO) and NO output (VNO) obtained with the NO monitoring system were significantly correlated with "alveolar" NO concentration (aNO) and exhaled NO volume from the simulator. Then, exhaled NO was measured in 12 thoracic surgery patients who underwent OLV using this system. pNO and VNO were significantly decreased by about half during OLV, and returned to baseline 25 min after releasing OLV. These data suggest that the newly designed online exhaled NO measuring system accurately detected aNO and exhaled NO volume in a breath-by-breath manner, and OLV for about 3 h did not influence the NO output from the lung after releasing OLV in thoracic surgery patients

A nocturnal decline of salivary pH associated with airway hyperresponsiveness in asthma

Salivary pH is associated with esophageal acid reflux and neutralization of esophageal acid. In this study, we assessed the association between nocturnal decline of salivary pH and airway hyperresponsiveness. Salivary pH was serially assessed in 9 patients with mild asthma (7 men and 2 women ;mean age 33.3 years ;mean %predicted FEV1.0 89.4%) and 10 healthy volunteers (6 men and 4 women ; mean age 31.2 years) using a pH indicator tape. The buffering capacity of saliva was defined as the median effective dose (ED50) for acidification of saliva with 0.01 N HCl, and airway responsiveness was defined as the dose of methacholine producing a 35% fall in Grs (PD35-Grs). There was a significant correlation between the values obtained from the pH indicator tape and those obtained from the electrometric pH meter. Using the indicator tape for sequential monitoring, we observed a nocturnal fall (pH) in salivary pH in all subjects. A significant correlation was found between airway hyperresponsiveness (PD35-Grs) and eitherpH or ED50 in mildly asthmatic patients. Vagal reflux dysfunction might contribute to nocturnal salivary pH as well as to airway hyperresponsiveness in mild asthmatics

Impact of serum retinol-binding protein 4 levels on regulation of remnant-like particles triglyceride in type 2 diabetes mellitus

Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m2, waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9 %). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = - 0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM. © 2013 Naoto Yamaaki et al

Clinical Study Impact of Serum Retinol-Binding Protein 4 Levels on Regulation of Remnant-Like Particles Triglyceride in Type 2 Diabetes Mellitus

Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7±4.1 kg/m 2 , waist circumference (WC) 88.4±10.7 cm, and HbA1c (NGSP) 7.2±1.9%). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG ( = 0.2544 and = 0.0056), TG ( = 0.1852 and = 0.041), RLP-TG/TG ( = 0.23765 and = 0.0241), and age ( = −0.2082 and = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG ( = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM

Difference of health-care associated pneumonia between large hospitals and small hospitals in Japan

Objective : Health-care associated pneumonia (HCAP) is a new category of pneumonia. We investigated differences of epidemiology, pathogens, and outcomes between HCAP patients in large hospitals and those in small hospitals. Methods : This was a retrospective observational study of patients hospitalized with HCAP from December 2009 to March 2010. HCAP was defined according to ATS/IDSA criteria. A large hospital was defined as 200 beds and a small hospital was 200 beds. Results : Of 117 patients, 61 patients were admitted to large hospitals and 56 patients were admitted to small hospitals. There was a significant difference of HCAP diagnostic criteria between the two groups. The A-DROP severity class was worse in the large hospital group than the small hospital group (P 0.05). Respiratory failure and disturbance of consciousness were more frequent in the large hospital group (P 0.05). The mortality rate was 8.2% in the large hospital group versus 1.8% in the small hospital group. Patients in the very severe A-DROP class had a high mortality rate of 33% in both groups. Conclusion : Patients with severe HCAP were more likely to be admitted to large hospitals. Patients in the very severe A-DROP class should receive intensive antibiotic therapy, but not all patients need broad-spectrum therapy

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe