General Anesthetics Inhibit Erythropoietin Induction under Hypoxic Conditions in the Mouse Brain

Background: Erythropoietin (EPO), originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS). EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes. Methodology/Principal Findings: BALB/c mice were exposed to 10 % oxygen with isoflurane at various concentrations (0.10–1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2a protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2a protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2a protein and EPO mRNA. Conclusions/Significance: Taken together, our results indicate that general anesthetics suppress activation of HIF-2 an

Orthostatic intolerance during early mobilization following video-assisted thoracic surgery.

[Purpose]Early postoperative mobilization is crucial for early ambulation to reduce postoperative pulmonary complications after lung resection. However, orthostatic intolerance (OI) may delay patient recovery, leading to complications. It is therefore important to understand the prevalence of and predisposing factors for OI following video-assisted thoracic surgery (VATS), which have not been established. This study evaluated the incidence of OI, impact of OI on delayed ambulation, and predisposing factors associated with OI in patients after VATS. [Methods]This retrospective cohort study consecutively analyzed data from 236 patients who underwent VATS. The primary outcome was defined as OI with symptoms associated with ambulatory challenge on postoperative day 1 (POD1), including dizziness, nausea and vomiting, feeling hot, blurred vision, or transient syncope. Multivariate logistic regression was performed to identify independent factors associated with OI. [Results]Of the 236 patients, 35.2 % (83) experienced OI; 45.8 % of these could not ambulate at POD1, compared with 15.7 % of patients without OI (P < 0.001). Factors independently associated with OI included advanced age [odds ratio 2.83 (1.46–5.58); P = 0.002], female gender [odds ratio 2.40 (1.31–4.46); P = 0.004], and postoperative opioid use [odds ratio 2.61 (1.23–5.77); P = 0.012]. Use of thoracic epidural anesthesia was not independently associated with OI [odds ratio 0.72 (0.38–1.37); P = 0.318]. [Conclusion]Postoperative OI was common in patients after VATS and significantly associated with delayed ambulation. Advanced age, female gender, and postoperative opioid use were identified as independent predisposing factors for OI

Preoperative Hypercapnia as a Predictor of Hypotension during Anesthetic Induction in Lung Transplant Recipients

【Objective】 To determine the incidence and predisposing factors of hypotension during anesthetic induction in lung transplant recipients. 【Design】 Retrospective study. 【Setting】 University hospital. 【Participants】 Patients who underwent lung transplantation between 2008 and 2013 (n = 68). 【Interventions】None. 【Measurements and Main Results】 The authors analyzed the mean arterial pressure (MAP) from administration of anesthetic drugs to 10 minutes after endotracheal intubation (ie, the anesthetic induction) among participants who underwent lung transplantation. Patients were considered to have clinically significant hypotension (CSH) when the following criteria were fulfilled: An MAP decrease of>40% from baseline and MAP of<60 mmHg. Overall, 41.2% of patients experienced CSH during the induction of anesthesia. The preoperative partial pressure of carbon dioxide (PaCO2) was significantly higher in patients who experienced CSH during anesthetic induction than in those who did not (p = 0.005). Preoperative PaCO2 predicted the development of CSH during anesthetic induction (area under the curve = 0.702; p = 0.002), with an optimal cut-off point of 55 mmHg determined by maximizing the Youden index. The incidences of CSH during anesthetic induction for patients with (PaCO2≥55) and without (PaCO2<55) preoperative hypercapnia were 75.0% (95% confidence interval [CI] [53.8-89.2]) and 30.8% (95% CI 26.4-37.3), respectively. After adjustment for known predicting factors, the odds ratio for the relationship between preoperative hypercapnia and CSH during anesthetic induction was 12.54 (95% CI 3.10-66.66). 【Conclusions】 Hypotension during anesthetic induction is common in lung transplant recipients, and is independently predicted by preoperative hypercapnia

Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner

Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions. Genes upregulated by HIF-1, including vascular endothelial growth factor and regulated in development and DNA damage response 1, both of which are involved in smoking-induced emphysematous changes, were increased by CSE treatment under non-hypoxic conditions in vitro and in vivo. Further investigation revealed that reactive oxygen species were generated in cells exposed to CSE and were required for CSE-mediated induction of HIF-1α protein, as was activation of phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. In conclusion, we demonstrated that CSE and CS induced HIF-1 activation in vitro and in vivo, respectively. The evidence warrants further investigation to indicate that HIF-1 plays an important role in CS-induced gene expression, which is deeply involved in pulmonary cellular stress and small airway remodelling

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation

Purpose: We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. Methods: Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. Results: The incidence of oxygen desaturation (SpO2 2; r = −0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. Conclusions: Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn

Additional file 1: of Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study

The dataset included the patient profiles, comorbidities, medications, and laboratory data at dialysis initiation. (XLSX 202 kb

Combination of brain natriuretic peptide and urinary albumin as a predictor of cardiovascular–renal events in outpatients with chronic kidney disease

Objectives: Cardiovascular and renal diseases are closely related. Brain natriuretic peptide (BNP) and urinary albumin are established predictors for cardiac and renal morbidities, respectively. To date, no reports have investigated the combined predictive value of BNP and urinary albumin for long-term cardiovascular–renal events in patients with chronic kidney disease (CKD). The aim of this study was to investigate this theme. Methods: Four hundred eighty-three patients with CKD were enrolled into this study and followed-up for 10 years. The endpoint was cardiovascular–renal events. Results: During the median follow-up period of 109 months, 221 patients developed cardiovascular–renal events. Log-transformed BNP and urinary albumin were identified as independent predictors for cardiovascular–renal events, with a hazard ratio of 2.59 (95% confidence interval [CI], 1.81–3.72) and 2.27 (95% CI, 1.82–2.84) for BNP and urinary albumin, respectively. For the combined variables, the group with high BNP and urinary albumin had a markedly higher risk (12.41-times; 95% CI 5.23–29.42) of cardiovascular–renal events compared with that of the group with low BNP and urinary albumin. Adding both variables to a predictive model with basic risk factors improved the C-index (0.767, 0.728 to 0.814, p=0.009), net reclassification improvement (0.497, p<0.0001), and integrated discrimination improvement (0.071, p<0.0001) more than each of them alone. Conclusions: This is the first report to demonstrate that the combination of BNP and urinary albumin can stratify and improve the predictability of long-term cardiovascular–renal events in CKD patients