Interaction of the hydrogen sulfide system with the oxytocin system in the injured mouse heart

Both the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) and oxytocin/oxytocin receptor (OT/OTR) systems have been reported to be cardioprotective. H2S can stimulate OT release, thereby affecting blood volume and pressure regulation. Systemic hyper-inflammation after blunt chest trauma is enhanced in cigarette smoke (CS)-exposed CSE−/− mice compared to wildtype (WT). CS increases myometrial OTR expression, but to this point, no data are available on the effects CS exposure on the cardiac OT/OTR system. Since a contusion of the thorax (Txt) can cause myocardial injury, the aim of this post hoc study was to investigate the effects of CSE−/− and exogenous administration of GYY4137 (a slow release H2S releasing compound) on OTR expression in the heart, after acute on chronic disease, of CS exposed mice undergoing Txt.Methods: This study is a post hoc analysis of material obtained in wild type (WT) homozygous CSE−/− mice after 2-3 weeks of CS exposure and subsequent anesthesia, blast wave-induced TxT, and surgical instrumentation for mechanical ventilation (MV) and hemodynamic monitoring. CSE−/− animals received a 50 μg/g GYY4137-bolus after TxT. After 4h of MV, animals were exsanguinated and organs were harvested. The heart was cut transversally, formalin-fixed, and paraffin- embedded. Immunohistochemistry for OTR, arginine-vasopressin-receptor (AVPR), and vascular endothelial growth factor (VEGF) was performed with naïve animals as native controls.Results: CSE−/− was associated with hypertension and lower blood glucose levels, partially and significantly restored by GYY4137 treatment, respectively. Myocardial OTR expression was reduced upon injury, and this was aggravated in CSE−/−. Exogenous H2S administration restored myocardial protein expression to WT levels.Conclusions: This study suggests that cardiac CSE regulates cardiac OTR expression, and this effect might play a role in the regulation of cardiovascular function

Intravenous hydrogen sulfide does not induce neuroprotection after aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury in a human-like porcine model of ubiquitous arteriosclerosis

Abstract Objective In rodents, intravenous sulfide protected against spinal cord ischemia/reperfusion (I/R) injury during aortic balloon occlusion. We investigated the effect of intravenous sulfide on aortic occlusion-induced porcine spinal cord I/R injury. Methods Anesthetized and mechanically ventilated “familial hypercholesterolemia Bretoncelles Meishan” (FBM) pigs with high-fat-diet-induced hypercholesterolemia and atherosclerosis were randomized to receive either intravenous sodium sulfide 2 h (initial bolus, 0.2 mg kg body weight (bw)−1; infusion, 2 mg kg bw−1 h−1; n = 4) or vehicle (sodium chloride, n = 4) prior to 45 min of thoracic aortic balloon occlusion and for 8 h during reperfusion (infusion, 1 mg kg bw−1 h−1). During reperfusion, noradrenaline was titrated to maintain blood pressure at above 80% of the baseline level. Spinal cord function was assessed by motor evoked potentials (MEPs) and lower limb reflexes using a modified Tarlov score. Spinal cord tissue damage was evaluated in tissue collected at the end of experiment using hematoxylin and eosin and Nissl staining. Results A balloon occlusion time of 45 min resulted in marked ischemic neuron damage (mean of 16% damaged motoneurons in the anterior horn of all thoracic motor neurons) in the spinal cord. In the vehicle group, only one animal recovered partial neuronal function with regain of MEPs and link motions at each time point after deflating. All other animals completely lost neuronal functions. The intravenous application of sodium sulfide did not prevent neuronal cell injury and did not confer to functional recovery. Conclusion In a porcine model of I/R injury of the spinal cord, treatment with intravenous sodium sulfide had no protective effect in animals with a pre-existing arteriosclerosis

Impaired Glucocorticoid Receptor Signaling Aggravates Lung Injury after Hemorrhagic Shock

We previously showed that attenuated lung injury after hemorrhagic shock (HS) coincided with enhanced levels of the glucocorticoid (GC) receptor (GR) in lung tissue of swine. Here, we investigated the effects of impaired GR signaling on the lung during resuscitated HS using a dysfunctional GR mouse model (GRdim/dim). In a mouse intensive care unit, HS led to impaired lung mechanics and aggravated lung inflammation in GRdim/dim mice compared to wildtype mice (GR+/+). After HS, high levels of the pro-inflammatory and pro-apoptotic transcription factor STAT1/pSTAT1 were found in lung samples from GRdim/dim mice. Lungs of GRdim/dim mice revealed apoptosis, most likely as consequence of reduced expression of the lung-protective Angpt1 compared to GR+/+ after HS. RNA-sequencing revealed increased expression of pro-apoptotic and cytokine-signaling associated genes in lung tissue of GRdim/dim mice. Furthermore, high levels of pro-inflammatory cytokines and iNOS were found in lungs of GRdim/dim mice. Our results indicate impaired repression of STAT1/pSTAT1 due to dysfunctional GR signaling in GRdim/dim mice, which leads to increased inflammation and apoptosis in the lungs. These data highlight the crucial role of functional GR signaling to attenuate HS-induced lung damage

Hyperoxia toxicity in septic shock patients according to the Sepsis-3 criteria: a post hoc analysis of the HYPER2S trial

Abstract Background Criteria for the Sepsis-3 definition of septic shock include vasopressor treatment to maintain a mean arterial pressure > 65 mmHg and a lactate concentration > 2 mmol/L. The impact of hyperoxia in patients with septic shock using these criteria is unknown. Methods A post hoc analysis was performed of the HYPER2S trial assessing hyperoxia versus normoxia in septic patients requiring vasopressor therapy, in whom a plasma lactate value was available at study inclusion. Mortality was compared between patients fulfilling the Sepsis-3 septic shock criteria and patients requiring vasopressors for hypotension only (i.e., with lactate ≤ 2 mmol/L). Results Of the 434 patients enrolled, 397 had available data for lactate at inclusion. 230 had lactate > 2 mmol/L and 167 ≤ 2 mmol/L. Among patients with lactate > 2 mmol/L, 108 and 122 were “hyperoxia”- and “normoxia”-treated, respectively. Patients with lactate > 2 mmol/L had significantly less COPD more cirrhosis and required surgery more frequently. They also had higher illness severity (SOFA 10.6 ± 2.8 vs. 9.5 ± 2.5, p = 0.0001), required more renal replacement therapy (RRT), and received vasopressor and mechanical ventilation for longer time. Mortality rate at day 28 was higher in the “hyperoxia”-treated patients with lactate > 2 mmol/L as compared to “normoxia”-treated patients (57.4% vs. 44.3%, p = 0.054), despite similar RRT requirements as well as vasopressor and mechanical ventilation-free days. A multivariate analysis showed an independent association between hyperoxia and mortality at day 28 and 90. In patients with lactate ≤ 2 mmol/L, hyperoxia had no effect on mortality nor on other outcomes. Conclusions Our results suggest that hyperoxia may be associated with a higher mortality rate in patients with septic shock using the Sepsis-3 criteria, but not in patients with hypotension alone

Surgical tracheostomy in a cohort of COVID-19 patients

Background!#!One of the main symptoms of severe infection with the new coronavirus‑2 (SARS-CoV-2) is hypoxemic respiratory failure because of viral pneumonia with the need for mechanical ventilation. Prolonged mechanical ventilation may require a tracheostomy, but the increased risk for contamination is a matter of considerable debate.!##!Objective!#!Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19.!##!Study design!#!Retrospective observational study between March 27 and May 18, 2020, in a single-center coronavirus disease-designated ICU at a tertiary care German hospital.!##!Patients!#!Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation.!##!Measurements!#!Clinical and ventilation data were obtained from medical records in a retrospective manner.!##!Results!#!A total of 18 patients with confirmed SARS-CoV‑2 infection and surgical tracheostomy were analyzed. The age range was 42-87 years. All patients received open tracheostomy between 2-16 days after admission. Ventilation after tracheostomy was less invasive (reduction in PEAK and positive end-expiratory pressure [PEEP]) and lung compliance increased over time after tracheostomy. Also, sedative drugs could be reduced, and patients had a reduced need of norepinephrine to maintain hemodynamic stability. Six of 18 patients died. All surgical staff were equipped with N99-masks and facial shields or with powered air-purifying respirators (PAPR).!##!Conclusion!#!Our data suggest that open surgical tracheostomy can be performed without severe complications in patients with COVID-19. Tracheostomy may reduce invasiveness of mechanical ventilation and the need for sedative drugs and norepinehprine. Recommendations for personal protective equipment (PPE) for surgical staff should be followed when PPE is available to avoid contamination of the personnel

Advanced photonic sensors based on interband cascade lasers for real-time mouse breath analysis

A multiparameter gas sensor based on distributed feedback interband cascade lasers emitting at 4.35 μm and ultrafast electro-spun luminescence oxygen sensors has been developed for the quantification and continuous monitoring of 13CO2/12CO2 isotopic ratio changes and oxygen in exhaled mouse breath samples. Mid-infrared absorption spectra for quantitatively monitoring the enrichment of 13CO2 levels were recorded in a miniaturized dual-channel substrate-integrated hollow waveguide using balanced ratiometric detection, whereas luminescence quenching was used for synchronously detecting exhaled oxygen levels. Allan variance analysis verified a CO2 measurement precision of 1.6‰ during a 480 s integration time. Routine online monitoring of exhaled mouse breath was performed in 14 mechanically ventilated and instrumented mice and demonstrated the feasibility of online isotope-selective exhaled breath analysis within microliters of probed gas samples using the reported combined sensor platform