Lung Inflation Research Articles

Abstract Su305: Chest Compression Fraction, Bag-mask Ventilation, And Survival From Out-of-hospital Cardiac Arrest: A Multicenter Study

Background: Ventilation during cardiopulmonary resuscitation (CPR) is poor. Better lung inflation during chest compression pauses is associated with better return of spontaneous circulation (ROSC), survival, and functional neurological survival. Chest compression quality, quantified by chest compression fraction (CCF) >80%, has also served as a guideline target for improved outcomes. We hypothesized that greater chest compression fraction modifies the association between ventilation quality and outcomes. Methods: We studied patients suffering out-of-hospital cardiac arrest from six sites of the Resuscitation Outcomes Consortium (ROC) Trial of Continuous or Interrupted Chest Compressions during CPR. We performed a subanalysis of patients assigned to the 30:2 CPR arm with ≥ two minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ohm (corresponding to ≥ 250 ml tidal volume) and duration ≥1 sec. We defined a chest compression pause as a break in chest compressions of 3 - 15 sec duration. We dichotomized ventilation into two groups: 1) better lung inflation (≥ one lung inflation waveform in ≥50% of chest compression pauses), and 2) poor lung inflation (waveforms in <50% pauses). We analyzed CCF during bag-mask prior to intubation (if any). We used multivariable logistic regression to assess the relationship among CCF, ventilation, and the outcomes of ROSC, survival, and functional neurologic survival. Results: Among 1,976 patients, mean age was 65 years, 66% were male. Most patients received poor ventilation (60%, n=1177) over ventilation over 9.8 ± 4.9 minutes. Median CCF was 0.78 (0.71, 90.84) and 0.78 (0.70, 0.83) for poor and better lung inflation, respectively. For CCF <85%, survival was significantly greater in those who received better ventilation, when compared to poor ventilation, and had greater pauses per minute (Figure A). The beneficial interaction between ventilation and outcome was greater with CCFs of 85% or less, compared to higher CCFs (Figure B). With CCFs >85%, survival did not improve significantly with better ventilation. These results persisted after adjustment for Ustein variables and ROC site. Conclusions: We observed improved survival with better ventilation until CCF exceeded 85% in the preintubation period, suggesting an optimal strategy with better ventilation and chest compression fractions of 85% or less.

The combination of postmortem sevoflurane ventilation and in situ topical cooling provides improved 6 hours lung preservation in an uncontrolled DCD porcine model

BackgroundRecent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model. MethodsAfter uDCD induction, donor pigs were allocated to one of the following groups: Control – static lung inflation only (SLI); TC – SLI + continuous intrapleural topical cooling (TC); or TC+Sevo – SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation. ResultsAnimals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion. ConclusionPreservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.

Risk of postoperative pneumonia after extubation with the positive pressure versus normal pressure technique: a single-center retrospective observational study.

A normal pressure extubation technique (no lung inflation before extubation), proposed by the Japanese Society of Anesthesiologists to prevent droplet infection during the coronavirus disease 2019 (COVID-19) pandemic, could theoretically increase postoperative pneumonia incidence compared with a positive pressure extubation technique (lung inflation before extubation). However, the normal pressure extubation technique has not been adequately evaluated. This study compared postoperative pneumonia incidence between positive and normal pressure extubation techniques using a dataset from the University of Tsukuba Hospital. In our hospital, the extubation methods changed from positive to normal pressure extubation techniques on March 3, 2020 due to the COVID-19 pandemic. Thus, we compared the risk of postoperative pneumonia between the positive (April 1, 2017 to December 31, 2019) and normal pressure extubation techniques (March 3, 2020 to March 31, 2022) using propensity score analyses. Postoperative pneumonia was defined using the International Classification of Diseases, 10th Edition (ICD-10) codes (J13-J18), and we reviewed the medical records of patients flagged with these ICD-10 codes (preoperative pneumonia and ICD-10 codes for prophylactic antibiotic prescriptions for pneumonia). We identified 20,011 surgeries, including 11,920 in the positive pressure extubation group (mean age 48.2years, standard deviation [SD] 25.2years) and 8,091 in the normal pressure extubation group (mean age 47.8years, SD 25.8years). The postoperative pneumonia incidences were 0.19% (23/11,920) and 0.17% (14/8,091) in the positive and normal pressure extubation groups, respectively. The propensity score analysis using inverse probability weighting revealed no significant difference in postoperative pneumonia incidence between the two groups (adjusted odds ratio 0.98, 95% confidence interval 0.50 to 1.91, P = 0.94). These results indicated no increased risk of postoperative pneumonia associated with the normal pressure extubation technique compared with the positive pressure extubation technique. Clinical trial number: UMIN000048589 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000055364.

Delayed sustained lung inflation for preterm neonates in neonatal intensive care unit: a randomized controlled trial

IntroductionSustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU).MethodsPreterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth.ResultsA total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia.ConclusionOur findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size.Trial registrationUniversity hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered).

Mechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model.

Mechanical ventilation exposes the lung to injurious stresses and strains that can negatively affect clinical outcomes in acute respiratory distress syndrome or cause pulmonary complications after general anesthesia. Excess global lung strain, estimated as increased respiratory system driving pressure, is associated with mortality related to mechanical ventilation. The role of small-dimension biomechanical factors underlying this association and their spatial heterogeneity within the lung are currently unknown. Using four-dimensional computed tomography with a voxel resolution of 2.4 cubic millimeters and a multiresolution convolutional neural network for whole-lung image segmentation, we dynamically measured voxel-wise lung inflation and tidal parenchymal strains. Healthy or injured ovine lungs were evaluated as the mechanical ventilation positive end-expiratory pressure (PEEP) was titrated from 20 to 2 centimeters of water. The PEEP of minimal driving pressure (PEEPDP) optimized local lung biomechanics. We observed a greater rate of change in nonaerated lung mass with respect to PEEP below PEEPDP compared with PEEP values above this threshold. PEEPDP similarly characterized a breaking point in the relationships between PEEP and SD of local tidal parenchymal strain, the 95th percentile of local strains, and the magnitude of tidal overdistension. These findings advance the understanding of lung collapse, tidal overdistension, and strain heterogeneity as local triggers of ventilator-induced lung injury in large-animal lungs similar to those of humans and could inform the clinical management of mechanical ventilation to improve local lung biomechanics.

Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs.

Gas flow is fundamental for driving tidal ventilation and, thus, the speed of lung motion, but current bias flow settings to support the preterm lung after birth do not have an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not affect lung mechanics, mechanical power, or gas exchange compared with those currently used in clinical practice (8-10 L/min). Speed of pressure and volume change during inflation were faster with higher flow rates. Lower flow rates resulted in less bronchoalveolar fluid protein, better lung morphology, and fewer detached epithelial cells. Overall, relative to unventilated fetal controls, there was greater protein change using 8-10 L/min, which was associated with enrichment of acute inflammatory and innate responses. Slowing the speed of lung motion by supporting the preterm lung from birth with lower flow rates than in current clinical use resulted in less lung injury without compromising tidal ventilation or gas exchange.

Impaired diffusion at submaximal lung inflation in asthma and copd patients

IntroductionDissolved-phase 129Xe MRI metrics suggest that gas diffusion may be more compromised at submaximal lung inflation compared to maximal inflation. We hypothesized that this diffusion deficit could be detected by comparing the carbon monoxide transfer coefficient (Kco) at submaximal lung inflation to that measured routinely at total lung capacity (TLC). MethodsAsthma and COPD patients performed carbon monoxide diffusion tests, first at maximal lung inflation for routine Kco and alveolar volume VA and then, at a 30 % reduced inflation (redux; obtaining Kcoredux and VAredux). At both inflations mixing efficiency was determined as VA/TLC and VAredux/TLCredux to examine a potential effect on Kcoredux/Kco behavior. ResultsIn normal subjects (n=36), median Kcoredux/Kco amounted to 130 [IQR:122–136]% as expected for normal Kco recruitment response. However, 60 % of asthma patients (49/83) and 80 % of COPD patients (44/55) showed reduced Kco recruitment at submaximal inflation (Kcoredux/Kco<122 %). In the asthma group, with otherwise normal routine Kco, Kcoredux/Kco was significantly correlated with RV/TLC ratio (r=-0.53;P<0.001), but not with VA/TLC. In COPD patients, all with abnormal routine Kco, abnormal Kcoredux/Kco response occurred in those patients with lower FEV1, higher RV/TLC and lower VA/TLC (P<0.01 for all). ConclusionSizeable portions of COPD and asthma patients showed a lack of normal Kco recruitment at submaximal lung inflation, related to high RV/TLC. In asthma, this was the case despite normal Kco at full lung inflation, suggesting that hyperinflation at lung volumes less than TLC affects the carbon monoxide diffusion rate constant by distorting pulmonary capillaries and alveolar–capillary membranes.

Association between emphysema and other pulmonary computed tomography patterns in primary varicella pneumonia: A retrospective cohort study.

This study aims to evaluate chest computed tomography (CT) findings in hospital patients with primary varicella pneumonia (PVP). We retrospectively analyzed CT images of 77 PVP patients using 3D Slicer, an open-source software, to model lesions and lungs. This retrospective cohort study was approved by the Institutional Review Board (Ethical Committee, Renmin Hospital, Hubei University of Medicine, Shiyan, China) and waived the requirement for written informed consent. The left lung was more frequently and severely affected in PVP, with significant differences between the 2 groups in CT involvement percentage of each lung region, except for total lung inflation. Group A showed higher median percentages of lung collapse compared to Group B. The extent of left lung involvement is a critical predictor of emphysema in PVP patients, highlighting the importance of also monitoring the right lung for more severe cases. Lower emphysema levels correspond to more collapsed and infiltrated lung segments, suggesting a more severe clinical presentation.

The Production, Assessment, and Utility of 3D-Printed Video Laryngoscopes in Eastern India: A Low-Cost Alternative to Conventional Video Laryngoscopes.

Introduction Recognizing the limitations of traditional direct laryngoscopes, particularly in difficult airway situations, video laryngoscopy has emerged as a potentially safer and more effective alternative. This study evaluated the utility of two 3D-printed video laryngoscopes: a standard geometry video laryngoscope (SGVL), resembling the traditional Macintosh blade, and a hyper-angulated video laryngoscope (HAVL) with a more curved design. Their performance was compared to a standard Macintosh direct laryngoscope across various intubation parameters. By leveraging the cost-effectiveness of 3D printing with polylactic acid, the study aimed to assess the potential of this technology to improve airway management across diverse clinical settings and varying levels of physician expertise. Methods This prospective randomized crossover study compared the effectiveness of 3D-printed video laryngoscopes (VL) and a standard direct laryngoscope in intubation. After obtaining IRB approval, physicians from various specialties across multiple centers participated. Participants received training on SGVL, HAVL, and DL intubation using an instructional video and hands-on practice. The training was standardized for all participants. The primary outcome measures were time to successful intubation, number of attempts, and time to visualize vocal cords. Participants were randomized to use all three laryngoscopes on a manikin, with a maximum of two attempts per scope. A 30-minute break separated each laryngoscope evaluation. Successful intubation was defined as the single insertion of each laryngoscope and bougie, followed by endotracheal tube placement and confirmation of lung inflation. Results Ninety-eight doctors, mostly from the EM team (73.5%) and ICU team (23.4%). Teams consist of consultants, residents, and medical officers of the concerned departments. Forty-eight of the participants (49%) were novice operators (<25 intubations). Successful first-attempt intubation in those with <1 year of experience with intubation (n=33) was highest for SGVL (97%) compared to DL (82%) and HAVL (67%). Participants who learned intubation through self-directed learning exhibited a higher acceptance of VL and achieved 100% success on their first attempt. Among those who followed modules or workshops, 97% had successful first-attempt intubation with VL. The average time taken to visualize the vocal cords was lower in SGVL compared to DL (5.6 vs. 7.5 seconds) (p<0.001). The HAVL also had a lower average time compared to the DL (7.1 vs. 7.5 secs) (p<0.001). However, the time taken to intubate using DL (24.2 ±8.7 sec) was similar to SGVL (28.1 ±13 sec). Lastly, the intubation time using HAVL was the longest (49.6 ±35.5 sec). The time to intubate with DL and SGVL had Spearman's rho of 0.64 (p<0.001), and DL and HAVL had 0.59 (p<0.001). Conclusions The ease of use and its cost-effective nature make 3D-printed VLs beneficial in situations where traditional VLs may not be available, especially in simulation and training.

Nodose afferent fibers require PIEZO2 for esophageal mechanosensation

The esophagus receives dual innervation of extrinsic afferent fibers from both the dorsal root ganglia as well as the vagal ganglia. These are polymodal sensory afferents that are able to sense a variety of stimuli that include chemical and mechanical stimuli. Previous research has demonstrated that the esophagus is innervated by low threshold mechanoreceptors arising from the nodose ganglia, which provide critical peripheral feedback that is required for proper swallowing and peristaltic reflexes. We know that in the vagal system, PIEZO2 plays a critical role in lung inflation and baroreceptor function in the aorta and carotid sinus. Hence, we hypothesize that PIEZO2 is the mechanotransducer in these nodose esophageal low threshold mechanoreceptors. We used a two-pronged approach to elucidate PIEZO2’s role in esophageal mechanosensation: first, GCaMP6s imaging and then single fiber electrophysiology to understand the kinetics of nodose esophageal afferent fiber activation. Both of these approaches used our ex-vivo intact vagal esophageal preparation. Our proof-of-principle studies were conducted in PIRT-GCaMP6s mice, obtained through the crossbreeding of Pirt-Cre (Cre expressed in all sensory neurons) mice with Cre-dependent, ROSA26 based, GCaMP6s reporter (B6.129S6-Gt(ROSA)26Sor-tm96(CAG-CGaMP6s)Hze). Our preliminary data in Pirt-GCaMP6s mice showed a profound increase in the Ca2+ influx in a subset of nodose neurons in response to mechanical distention of the esophagus at 5, 10, and 30mmHg pressures. For our knockout group, we obtained nodose-specific knockout of PIEZO2 by crossing P2X2-Cre mice (P2X2 is expressed in all nodose neurons) with PIEZO2fl/fl mice (P2X2/PIEZO2 KO mice). Upon performing our GCaMP6s imaging experiments in this group, we saw that there was a significant reduction in the number of nodose neurons that were responsive to esophageal distention (58% down to 17%). Comparing the fluorescence intensities of all esophageal neurons between the control and KO groups, we observed a significant reduction at all three intraesophageal pressures (p&lt;0.05, n=458 and 395 neurons in control and KO groups, respectively). In our single fiber electrophysiology experiments, our control and KO groups were PIEZO2fl/fl mice and P2X2/PIEZO2 KO respectively. We were able to successfully record APs from A-fiber mechanosensitive esophageal neurons. The number of APs recorded from KO group was reduced at all the three intraesophageal pressures when compared to the control PIEZO2fl/fl mice. Our findings support the hypothesis that PIEZO2 is the mechanotransduction protein involved in vagal nodose afferent fibers innervating the esophagus. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A modified orthotopic left lung transplantation model in rats

To enhance the operability of the rat orthotopic left lung transplantation model, we implemented several improvements and meticulously detailed the procedure. One hundred and thirty-one healthy male Sprague Dawley rats, weighing between 250 and 300 g, were utilized, with 64 serving as donors, 64 as recipients, and 3 as sham controls. We employed a modified three-cuff technique for the orthotopic left lung transplantation. Notably, our modified perfusion method could prevent donor lung edema, while waist-shaped cuffs minimized suture slippage during anastomosis. Additionally, positioning the recipient rat in a slightly left-elevated supine position during anastomosis reduced tension on the lung hilum, thus mitigating the risk of vascular laceration. The introduction of a unique two-person anastomosis technique significantly reduced operation time and substantially improved success rates. Furthermore, maximizing inflation of donor lungs both during preservation and surgery minimized the occurrence of postoperative atelectasis. Various other procedural refinements contributed to the enhanced operability of our model. Sixty-four rat orthotopic left lung transplantations were performed with only one surgical failure observed. The acquisition time for donor lungs averaged (19 ± 4) minutes, while (11 ± 1) minutes were allocated for donor lung hilum anatomy and cuff installation. Recipient thoracotomy and left lung hilar anatomy before anastomosis required (24 ± 8) minutes, with anastomosis itself taking (31 ± 6) minutes. Remarkably, the survival rate at the 4-h postoperative mark stood at 96.7 %. Even six months post-operation, transplanted left rat lungs continued to exhibit proper inflation and contraction rhythms, displaying signs of chronic pathological changes. In summary, our modified rat model of orthotopic left lung transplantation demonstrates robust operability, significantly reducing surgical duration, improving operation success rates, and enhancing postoperative survival rates. Furthermore, its long-term survival capacity enables the simulation of acute and chronic disease processes following lung transplantation.

Continuous and bilevel positive airway pressure may improve radiotherapy delivery in patients with intra-thoracic tumors

BackgroundMinimizing tumor motion in radiotherapy for intra-thoracic tumors reduces side-effects by limiting radiation exposure to healthy tissue. Continuous or Bilevel Positive Airway Pressure (CPAP/BiPAP) could achieve this, since it could increase lung inflation and decrease tidal volume variability. We aim to identify the better CPAP/BiPAP setting for minimizing tumor motion. MethodsIn 10 patients (5 with lung cancer, 5 with other intra-thoracic tumors), CPAP/BiPAP was tested with the following settings for 10 min each: CPAP 5, 10 and 15 cmH2O and BiPAP 14/10 cmH2O with a lower (7 breaths/min) and higher back-up respiratory rate (BURR initially 1 breath/min above the spontaneous breathing frequency, with the option to adjust if the patient continued to initiate breaths). Electrical impedance tomography was used to analyse end-expiratory lung impedance (EELI) as an estimate of end-expiratory lung volume and tidal impedance variation (TIV) as an estimate of tidal volume. ResultsNine out of ten patients tolerated all settings; one patient could not sustain CPAP-15. A significant difference in EELI was observed between settings (χ2 22.960, p < 0.001), with most increase during CPAP-15 (median (IQR) 1.03 (1.00 – 1.06), normalized to the EELI during spontaneous breathing). No significant differences in TIV and breathing variability were found between settings. ConclusionsThis study shows that the application of different settings of CPAP/BiPAP in patients with intra-thoracic tumors is feasible and tolerable. BiPAP with a higher BURR may offer the greatest potential for mitigating tumor motion among the applied settings, although further research investigating tumor motion should be conducted.

The Rat Thoracic Ultrasound protocol: scanning technique and normal findings.

Respiratory diseases (especially pneumonia) are very common disorders in pet rats. The suspected diagnosis is mostly based on the clinical signs, thoracic auscultation, and thoracic radiography. However, auscultation is insensitive in determining the severity of the disease, and radiographs are often unremarkable. Non-cardiac thoracic ultrasonography is increasingly used in veterinary medicine; however, it has not been described in detail in rats. Thoracic ultrasonic examination was conducted on 400 client-owned conscious pet rats. The rats were examined in the period from June 2023 to August 2023 in two veterinary clinics. Due to the small size of the animal, different anatomical considerations, and different evaluation protocols, as well as to meet the optimal outcome of detailed thoracic ultrasound, a standard methodological protocol was developed, and the name RATTUS (Rat Thoracic Ultrasound) was proposed. Typical signs of normal RATTUS were described (bat sign, lung sliding, A-lines, abdominal curtain sign, ski jump sign, lung pulse, seashore sign in M-mode, and bamboo sign). The new evaluation of lung inflation symmetry by substernal access was also described. The methodical approach presented and the normal findings description are proposed to be used for a standard/routine thoracic ultrasound examination in pet rats.

Discrepancy Between Achieved and Vendor-Predicted Ablation Zones in the Lung: Contributing Factors.

Several factors are known to affect lung ablation zones. Questions remain as to why there are discrepancies between achieved and vendor-predicted ablation zones and what contributing factors can be modified to balance therapeutic effects with avoidance of complications. This retrospective study of lung tumour microwave ablation analyses day 1 post-treatment CT to assess the effects of lesion-specific and operator-dependent factors on ablation zones. Consecutive patients treated at a tertiary centre from 2018 to 2021 were included. All ablations were performed using a single microwave ablation device under lung isolation. The lung tumours were categorised as primary or secondary, and their "resistance" to ablation was graded according to their locations. Intraprocedural pulmonary inflation was assessed as equal to or less than the contralateral non-isolated lung. Ablation energy was categorised as high, medium, or low. Ablation zone dimensions were measured on day 1 CT and compared to vendor reference charts. Ablations with multiple needle positions or indeterminate boundaries were excluded. A total of 47 lesions in 31 patients were analysed. Achieved long axes are longer than predicted by 5mm or 14% (p < 0.01) without overall short axis discrepancy. Secondary tumours (p = 0.020), low-resistance location (p < 0.01), good lung inflation (p < 0.01), low (p = 0.003) and medium (p = 0.038) total energy produce lengthened long axes by 4-6mm or 10-19%. High total energy results in shorter than predicated short axes by 6mm or 18% (p = 0.010). We identified several factors affecting ablation zone dimensions which may have implications for ablation planning and the avoidance of complications.

Evolution of interfacial mechanics of lung surfactant mimics progression of acute respiratory distress syndrome.

How acute respiratory distress syndrome progresses from underlying disease or trauma is poorly understood, and there are no generally accepted treatments resulting in a 40% mortality rate. However, during the inflammation that accompanies this disease, the phospholipase A2 concentration increases in the alveolar fluids leading to the hydrolysis of bacterial, viral, and lung surfactant phospholipids into soluble lysolipids. We show that if the lysolipid concentration in the subphase reaches or exceeds its critical micelle concentration, the surface tension, γ, of dipalmitoyl phosphatidylcholine (DPPC) or Curosurf monolayers increases and the dilatational modulus, [Formula: see text], decreases to that of a pure lysolipid interface. This is consistent with DPPC being solubilized in lysolipid micelles and being replaced by lysolipid at the interface. These changes lead to [Formula: see text] which is the criterion for the Laplace instability that can lead to mechanical instabilities during lung inflation, potentially causing alveolar collapse. These findings provide a mechanism behind the alveolar collapse and uneven lung inflation during ARDS.

Increased cardiac output and left ventricular contractility in pigs paced with vs. without restored respiratory sinus arrhythmia - proof of principle of a newly developed pacing device

Abstract Background Heart rate variability (HRV) correlates with the severity and mortality of heart failure. Respiratory sinus arrhythmia (RSA) is defined by the dynamic increase and decrease in heart rate between breaths. Restoration of RSA might be beneficial in patients with heart failure and/or patients in need of permanent pacing. Purpose The aim of this translational, proof-of-principle study was to investigate the effect of pacing with or without RSA using a newly designed pacing device on the left ventricular contractility and cardiac output. Methods The project was initiated with the aim of designing a new pacing device capable of restoring RSA in paced hearts with the help of lung inflation sensors. Neuronal networks were designed to reconstruct the human brain using ultra-low energy-consuming technology. The lung inflation sensor fed the detected inspiration data back to the pacing device, which paced the heart via pacing leads (DDD) in the right atrium and ventricle. In total, 5 intubated but spontaneously breathing landrace pigs were paced without RSA (fixed-rate pacing) and with restored RSA. Stroke volume and cardiac output were measured by echocardiography (diameter of left ventricular outflow tract and velocity time integral measured by pulsed wave doppler averaged over three heart beats). Preload-independent cardiac contractility was measured via a pressure-volume loop catheter in the left ventricle during occlusion of the inferior vena cava. Fig. 1 indicates the setup of the trial. The trials were conducted according to the relevant rules (NIH Publication no. 85-23 revised 1985) and in accordance with national law. Results Echocardiography (n=5) showed a mean left ventricular outflow tract diameter of 21 ± 0.1 mm. The mean intrinsic heart rate was 87 ± 14 bpm, and the mean paced heart rate was 104 ± 5 bpm in the pigs (65 ± 3 kg). The main outcomes are displayed in Fig. 2: The left ventricular stroke volume increased by 11ml (+21%, p=0.036) with 100% RSA compared to pacing without RSA, while cardiac output increased by 1.14 l/min (+21%, p=0.037). The pressure volume area is proportional to the total myocardial oxygen consumption and decreased by 6234 mmHg*ml (-39%, p=0.004). Cardiac efficiency represents the relative amount of blood being pumped consuming one unit energy and increased by 0.163 (+72%, p=0.033). End-systolic pressure volume relationship demonstrated a non-significant increase by 0.183 mmHg/ml (+45%, p=0.25). Parameters of diastolic function (Tau) did not differ between the groups. Conclusion Restoration of RSA by our newly developed pacing device significantly improved the cardiac contractility/output in our proof-of-principle large animal translational model. Chronic trials will be required to definitively confirm the positive effects of RSA on cardiac remodeling.Fig. 1: Set-up of the animal trials.Fig. 2: Main results (mean/std error)

Abstract 280: Effectiveness of Bag-Valve-Mask Ventilation During Out-of-Hospital Pediatric CPR

Background: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 15 or 30 chest compressions to deliver ventilations for children. The effectiveness of bag-valve-mask (BVM) ventilation delivered during the pause in chest compressions is unknown. Hypothesis: Lung inflation occurs infrequently with BVM ventilation during 30:2 (and 15:2) CPR. Aim: To determine the incidence of lung inflation with BVM ventilation during 15:2 or 30:2 CPR for pediatric OHCA. Methods: This is a retrospective, observational study of 63 OHCA patients, &lt;18 years of age, with non-traumatic cardiac arrest from the Dallas-Fort Worth Center for Resuscitation Research registry. Emergency medical service rescuers provided 30:2 or 15:2 CPR with BVM ventilation and ≥ 2 min of recorded CPR. We measured bioimpedance ventilation (lung inflation) waveforms in the pauses between chest compression segments recorded through defibrillation pads. A detectable ventilation waveform had a bioimpedance amplitude ≥0.5 Ohm and duration ≥1 sec. We measured the incidence of ventilation in two pre-specified groups: patients with ventilation waveforms in &lt;50% of pauses (Group 1) vs. those with waveforms in ≥50% of pauses (Group 2). Results: The mean duration of 30:2 or 15:2 CPR was 15(8) min prior to advanced airway placement. During this period, we identified 683 pauses in chest compressions, 386 measurable ventilations, and the median (IQR) number of ventilations was 2 (0-4). Of 20 advanced airway attempts, nine were successful.Group 1 (N=48) had a median 8 pauses and 1.5 ventilations/patient, Group 2 (N= 15) had a median 10 pauses and 12 ventilations/patient (Table). Return of spontaneous circulation for Group 1 (15%, 7/48) vs. Group 2 (33%, 5/15). Conclusion: This study shows that use of a BVM device results in infrequent lung inflation during 30:2 or 15:2 CPR in pediatric patients.

The role of lung volume recruitment therapy in neuromuscular disease: a narrative review.

Respiratory muscle weakness results in substantial discomfort, disability, and ultimately death in many neuromuscular diseases. Respiratory system impairment manifests as shallow breathing, poor cough and associated difficulty clearing mucus, respiratory tract infections, hypoventilation, sleep-disordered breathing, and chronic ventilatory failure. Ventilatory support (i.e., non-invasive ventilation) is an established and key treatment for the latter. As survival outcomes improve for people living with many neuromuscular diseases, there is a shift towards more proactive and preventative chronic disease multidisciplinary care models that aim to manage symptoms, improve morbidity, and reduce mortality. Clinical care guidelines typically recommend therapies to improve cough effectiveness and mobilise mucus, with the aim of averting acute respiratory compromise or respiratory tract infections. Moreover, preventing recurrent infective episodes may prevent secondary parenchymal pathology and further lung function decline. Regular use of techniques that augment lung volume has similarly been recommended (volume recruitment). It has been speculated that enhancing lung inflation in people with respiratory muscle weakness when well may improve respiratory system "flexibility", mitigate restrictive chest wall disease, and slow lung volume decline. Unfortunately, clinical care guidelines are based largely on clinical rationale and consensus opinion rather than level A evidence. This narrative review outlines the physiological changes that occur in people with neuromuscular disease and how these changes impact on breathing, cough, and respiratory tract infections. The biological rationale for lung volume recruitment is provided, and the clinical trials that examine the immediate, short-term, and longer-term outcomes of lung volume recruitment in paediatric and adult neuromuscular diseases are presented and the results synthesised.

Geometric and network organization of visceral organ epithelium.

Mammalian epithelia form a continuous sheet of cells that line the surface of visceral organs. To analyze the epithelial organization of the heart, lung, liver and bowel, epithelial cells were labeled in situ, isolated as a single layer and imaged as large epithelial digitally combine montages. The stitched epithelial images were analyzed for geometric and network organization. Geometric analysis demonstrated a similar polygon distribution in all organs with the greatest variability in the heart epithelia. Notably, the normal liver and inflated lung demonstrated the largest average cell surface area (p < 0.01). In lung epithelia, characteristic wavy or interdigitated cell boundaries were observed. The prevalence of interdigitations increased with lung inflation. To complement the geometric analyses, the epithelia were converted into a network of cell-to-cell contacts. Using the open-source software EpiGraph, subgraph (graphlet) frequencies were used to characterize epithelial organization and compare to mathematical (Epi-Hexagon), random (Epi-Random) and natural (Epi-Voronoi5) patterns. As expected, the patterns of the lung epithelia were independent of lung volume. In contrast, liver epithelia demonstrated a pattern distinct from lung, heart and bowel epithelia (p < 0.05). We conclude that geometric and network analyses can be useful tools in characterizing fundamental differences in mammalian tissue topology and epithelial organization.

Perinatal ethanol exposure alters respiratory chemoreflex responses in anesthetized rats

In the USA 10-15% of pregnant women drink alcohol (ethanol) leading to a variable compilation of developmental abnormalities, including deficits in critical homeostatic functions such as poor coordination of suckling, breathing, and swallowing. Here, we test the hypothesis that perinatal ethanol exposure alters respiratory chemoreflex responses in neonatal rats. Pregnant rats were exposed to 5% ethanol through their drinking water starting on embryonic day 5, which exposes the fetuses to ethanol during gestation and then after birth through the breast milk. Pups of both sexes were studied in the first week of life (postnatal days (P) 1-5). First, in awake pups, we used head-out plethysmography to assess the effects of ethanol exposure on the respiratory response to a brief, 5- minute episode of hypoxic hypercapnia (12% O2/5% CO2, balance N2, delivered through a nose cone). We found no significant differences in the frequency (P = 0.6667), tidal volume (P = 0.3627), or minute ventilation (P = 0.1582) responses to the challenge between control and ethanol exposed pups (2-way ANOVA, n = 6 control and 6 ethanol pups). In a second experiment, we used electromyography in anesthetized pups to study the diaphragm and tongue muscle responses to nasal occlusion, which results in strong muscle efforts but an absence of lung inflation, as well as hypoxia, hypercapnia, and acidosis. Here, we found that both diaphragm and tongue muscle EMG responses were significantly blunted in ethanol exposed animals compared to control. This included a decrease in the peak amplitude responses of both muscles (2-way ANOVA: diaphragm, P = 0.0175; tongue, P= 0.0317, n = 8 control and 8 ethanol pups), as well as a delay in the onset of the tongue muscle activation (Student’s unpaired T-test, P = 0.0219, n = 8 control and 8 ethanol pups). Together, these data indicate that perinatal ethanol exposure causes impairments in respiratory chemoreflex control, which appear to be highly dependent on level of arousal. NIH 5R01HD071302-08 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.