Pulmonary Shunt Research Articles

Reduced fetal ductus venosus shunt fraction is associated with adverse perinatal outcomes in pregnancy with pregestational diabetes mellitus.

We aimed to determine fetal liver perfusion in PGDM and GDM pregnancies and to assess the relation of ductus venosus (DV) shunt fraction with adverse pregnancy outcomes. We conducted a prospective longitudinal observational study including 188 pregnant women: group I-patients with pregestational DM (PGDM, n = 86), group II-patients with gestational DM (GDM, n = 44), group III-control (n = 58). The patients included in the study underwent ultrasound examination at 30+0-40+0weeks of pregnancy. We evaluated volumetric blood flow adjusted to EFW (Q, ml/min/kg) for umbilical vein, DV, left and main portal vein. The relative risk was calculated for adverse pregnancy outcomes. In PGDM pregnancies, umbilical blood flow was redistributed to the fetal liver, increasing left portal and total liver volumetric blood flow (p < 0.001) compared with GDM and control groups. Pathological reduction in the DV shunt fraction (≤ 16.5%) was associated with an increased relative risk of preterm delivery (3.61 [95%CI 1.68; 7.71]), LGA-birth (1.64 [95% CI 1.26; 2.12]), neonatal adiposity (1.53 [95%CI 1.18; 1.98]), fetal hypoxia (3.47 [95%CI 1.34; 9.05]), emergency cesarean Sect.(1.93 [95%CI 1.26; 2.97]), and neonatal intensive care unit stay of more than 5days (1.78 [95%CI 1.08; 2.93]). Decreased DV shunt fraction reflects changes in fetal hemodynamics in PGDM-pregnancies and associated with an increased risk of adverse perinatal outcomes.

Distribution and role of peripheral arterial chemoreceptors in cardio-respiratory control of the south american rattlesnake (Crotalus durissus).

Peripheral arterial chemoreceptors monitor the levels of arterial blood gases and adjust ventilation and perfusion to meet metabolic demands. These chemoreceptors are present in all vertebrates studied to date but have not been described fully in reptiles other than turtles. The goals of this study were to 1) identify functional chemosensory areas in the South American rattlesnake (Crotalus durissus) 2) determine the neurochemical content of putative chemosensory cells in these areas and 3) determine the role each area plays in ventilatory and cardiovascular control. To this end, rattlesnakes were instrumented with transonic flow probes, arterial catheters, and subcutaneous impedance electrodes to measure shunt fraction, heart rate, blood pressure and ventilation, respectively. The catheters were placed at three putative chemosensory sites, the bases of the aortic arch, pulmonary artery, as well as at the carotid bifurcation, for site specific activation with sodium cyanide (NaCN, 0.5mg/0.1ml). These same sites were subsequently examined using immunohistochemical markers for acetylcholine, tyrosine hydroxylase (TH, the rate limiting enzyme in catecholamine synthesis) and serotonin, to identify putative oxygen-sensing cells. All three sites were chemosensory and stimulating each led to cardiovascular (shunt fraction and heart rate) and respiratory adjustments although not in an identical fashion. All three chemosensory areas contained cells positive for serotonin (5-HT), however, cells positive for vesicular acetylcholine transporter (VAChT) were found only in the aorta and pulmonary artery. We found no labeling for TH at any site.

Evaluation of the therapeutic effects of nebulized inhalation of hydrogen-rich water on primary blast lung injury in C57BL/6 mice.

Primary blast lung injury is a common and severe consequence of explosion events, characterized by immediate and delayed effects such as apnea and rapid shallow breathing. The overpressure generated by blasts leads to alveolar and capillary damage, resulting in ventilation-perfusion mismatch and increased intrapulmonary shunting. This reduces the effective gas exchange area, causing hypoxemia and hypercapnia. Hydrogen (H2), a small-molecular-weight, nonpolar diatomic molecule, has shown potential in treating various diseases due to its antioxidant and anti-inflammatory properties. This study evaluates the therapeutic effects of nebulized hydrogen-rich water on primary blast lung injury in C57BL/6 mice and explores the underlying mechanisms. C57BL/6 mice (n= 150), aged 6-8weeks, were randomly divided into 2 groups: the blast injury control group (n= 75) and the nebulized hydrogen-rich water treatment group (n= 75). Mice were exposed to a blast overpressure of 266±9.156 kPA and treated with either nebulized hydrogen-rich water or sterile injection water immediately postinjury. Observations were made at 6, 12, 24, and 48hours postinjury. Lung function was assessed using whole-body plethysmography, and arterial blood gases were analyzed. Lung tissue was examined histologically and biochemically for markers of inflammation and oxidative stress. The survival rates at different time points postinjury in the nebulized hydrogen-rich water treatment group were significantly higher than those in the blast injury control group (6hours postinjury: 89.3% vs 78.6%; 12hours postinjury: 81.3% vs 72%; 24hours postinjury: 81.3% vs 61.3%, P < .01). Lung function tests revealed significant improvements in tidal volume (12hours postinjury: 0.11±0.018 vs 0.08±0.016, 24hours postinjury: 0.16±0.013 vs 0.12±0.013, 48hours postinjury: 0.18±0.02 vs 0.13±0.014), respiratory rate (6hours postinjury: 235.07±12.82 vs 268.29±13.73; 12hours postinjury: 265.47±10.06 vs 342.16±16.34; 24hours postinjury: 248.20±9.28 vs 352.80±15.99; 48hours postinjury: 226.12±15.81 vs 318.18±15.81), and minute ventilation (12hours postinjury: 22.05±3.46 vs 15.93±3.68; 24hours postinjury: 27.30±2.15 vs 21.62±2.48; 48hours postinjury: 37.48±3.93 vs 28.32±2.98) in the nebulized hydrogen-rich water treatment group (P < .01). Arterial blood gas analysis indicated better oxygenation and reduced hypercapnia in the nebulized hydrogen-rich water treatment group (P < .05). Histologic examination showed reduced lung edema and hemorrhage in the nebulized hydrogen-rich water treatment group. Levels of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α) and oxidative stress markers (ie, malondialdehyde) were significantly lower, whereas antioxidant enzyme (total superoxide dismutase) activity was higher in the nebulized hydrogen-rich water treatment group compared with the blast injury control group (P < .01). Arterial blood gas analysis indicated better oxygenation and reduced hypercapnia in the nebulized hydrogen-rich water treatment group (P < .05). Histologic examination showed reduced lung edema and hemorrhage in the nebulized hydrogen-rich water treatment group. Levels of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α) and oxidative stress markers (ie, malondialdehyde) were significantly lower, whereas antioxidant enzyme (total superoxide dismutase) activity was higher in the nebulized hydrogen-rich water treatment group compared with the blast injury control group (P < .01). Hydrogen-rich water treatment significantly improves survival rates and lung function and reduces inflammation and oxidative stress in mice with primary blast lung injury. These findings suggest that hydrogen's antioxidant and anti-inflammatory properties play a crucial role in mitigating lung damage and improving respiratory function postinjury. Further long-term studies and imaging analyses are needed to confirm these findings and elucidate the molecular mechanisms involved. This study provides a theoretical basis for the clinical application of hydrogen-rich water in treating blast-induced lung injuries.

Use of the oxygen reserve index/FiO2 as a non-invasive index to estimate venous admixture in anesthetized dogs.

The oxygen reserve index (ORi) is a novel, non-invasive parameter that estimates arterial oxygen partial pressure (PaO2) during hyperoxia when the fraction of inspired oxygen (FiO2) is elevated. This study aimed to assess the utility of the ORi/FiO2 ratio as an index for quantifying F-shunt, serving as an estimate of venous admixture. Anesthetic records were reviewed from 44 dogs undergoing general anesthesia and requiring arterial catheterization. ORi was measured via a CO-oximeter using a probe on the tongue. Paired measurements of PaO2, obtained by blood gas analysis, and ORi were taken at various FiO2 levels to achieve an ORi between 0 and 1. Venous admixture was quantified by F-shunt. Spearman's correlation coefficient assessed the relationship between ORi/FiO2 and F-shunt. Youden's index identified the optimal cut-off point to predict a physiological F-shunt (≤ 10%). A total of 77 paired observations were collected, revealing a moderate negative correlation between F-shunt and ORi/FiO2 (rho = -0.59, p < 0.001). An ORi/FiO2 cut-off of 1.2 demonstrated 80% sensitivity for identifying dogs with an F-shunt ≤10%, with a ROC curve area above 80%. However, the index was less effective at distinguishing dogs with higher shunt fractions. The ORi/FiO2 index identifies dogs with low F-shunt during anesthesia with strong sensitivity and predictive accuracy, potentially ruling out the occurrence of ventilation-perfusion inequality. However, it cannot replace blood gas analysis for quantifying venous admixture.

Predicting Time to First Rejection Episode in Lung Transplant Patients Using a Comprehensive Multi-Indicator Model.

Rejection hinders long-term survival in lung transplantation, and no widely accepted biomarkers exist to predict rejection risk. This study aimed to develop and validate a prognostic model using laboratory data to predict the time to first rejection episode in lung transplant recipients. Data from 160 lung transplant recipients were retrospectively collected. Univariate Cox analysis assessed the impact of patient characteristics on time to first rejection episode. Kaplan-Meier survival analysis, LASSO regression, and multivariate Cox analysis were used to select prognostic indicators and develop a riskScore model. Model performance was evaluated using Kaplan-Meier analysis, time-dependent ROC curves, and multivariate Cox regression. Patient characteristics were not significantly associated with the time to the first rejection episode. Six laboratory indicators-Activated Partial Thromboplastin Time, IL-10, estimated intrapulmonary shunt, 50% Hemolytic Complement, IgA, and Complement Component 3-were identified as significant predictors and integrated into the riskScore. The riskScore demonstrated good predictive performance. It outperformed individual indicators, was an independent risk factor for rejection, and was validated in the validation dataset. The riskScore model effectively predicts time to first rejection episode in lung transplant recipients.

Evaluation of long axial field-of-view (LAFOV) PET/CT for post-treatment dosimetry in Yttrium-90 radioembolization of liver tumors: a comparative study with conventional SPECT imaging.

Long axial field-of-view (LAFOV) positron emission tomography/computed tomography (PET/CT) scanners enable high sensitivity and wide anatomical coverage. Therefore, they seem ideal to perform post-selective internal radiation therapy (SIRT) 90Y scans, which are needed, to confirm that the dose is delivered to the tumors and that healthy organs are spared. However, it is unclear to what extent the use of LAFOV PET is feasible and which dosimetry approaches results in accurate measurements. In this retrospective analysis, a total number of 32 patients was included (median age 71, IQR 14), which had hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. All patients underwent SIRT, and the post-therapy scan was acquired on a single photon emission computed tomography/computed tomography (SPECT/CT) and a LAFOV Biograph Quadra PET/CT with a 20-minute acquisition time. Post-treatment dosimetry, regarding the tumor, whole-liver and lung (LMD) absorbed dose was done using an organ-wise (Simplicit90Y) and a voxel-wise approach (HERMIA Dosimetry) which used a semi-Monte Carlo algorithm. The lung shunt fraction (LSF) was also measured using the voxel-wise approach and compared to the planned. The planning, post-treatment SPECT and PET (SPECTpre, SPECTpost, PETpost) median tumor doses based on the organ-wise dosimetry were 276.0Gy (200.0-330.0Gy), 232.0Gy (158.5-303.5Gy) and 267.5Gy (182.5-370.8Gy). In contrast, the median voxel-wise PETpost dose was significantly smaller than the planned SPECTpre (152.5Gy (94.8-223.8Gy); p < 0.00001). Moreover, the median tumor absorbed dose at 90% (D90) of the tumor volume was significantly higher in SPECTpost compared with PETpost (123.5Gy; 81.5-180.0 vs. 30.5Gy; 11.3-106.3; p < 0.00001). The PETpost measured LSF was significantly lower compared to the planned SPECTpre (0.89%; 0.4-1.3% vs. 2.3%; 1.5-3.6%; p < 0.0001). Similarly, the measured PETpost median LMD was considerably lower to the planned SPECTpre (1.2Gy; 0.6-2.3 vs. 2.5Gy; 1.4-4.7; p < 0.0001). LAFOV PET enabled the direct measurement of post therapy lung dose and tumor doses that correlated well with the planned treatment doses. However, current voxel-wise-based tumor dosimetry seems to be inaccurate for LAFOV PET. In addition, dose volume histogram-based metrics also significantly underestimate the delivered dose. Therefore, improved dosimetry tools are needed for reliable voxel-wise 90Y dosimetry to leverage the sensitivity and spatial resolution of LAFOV PET scanners.

Effects of ultrasound-guided stellate ganglion block on intrapulmonary shunt and oxygenation in patients with single-lung ventilation

BackgroundSingle-lung ventilation (SLV) is a widely used procedure in thoracic surgery; however, it can lead to hypoxemia, which is attributed to intrapulmonary shunt and hypoxic pulmonary vasoconstriction. Stellate ganglion blockade (SGB) has shown protective effects during SLV in various pulmonary conditions. The objective of the study was to assess the clinical utility of ultrasound-guided SGB in patients undergoing thoracoscopic pulmonary lobectomy through a prospective clinical trial.MethodsThis prospective randomized controlled double-blind trial included 116 patients who underwent SLV. After exclusion, 88 patients were randomly assigned to either the SGB group (n = 40) or control group (n = 39), with the latter receiving no SGB. Hemodynamics using oxygenation index (OI) and the pulmonary shunt fraction (Qs/Qt), respiratory mechanics using dynamic lung compliance (Cdyn) and mean airway pressure (Pmean), and levels of pro-inflammatory factors (IL-6 and IL-8) were assessed as clinical outcomes after surgery.ResultsSLV induced upregulation of Pmean, Qs/Qt, and levels of IL-6 and IL-8 and downregulation of Cdyn and OI. Compared to the control group, the SGB group demonstrated significantly decreased Pmean, Qs/Qt, IL-6, and IL-8 and increased Cdyn and OI, suggesting the protective effects of SGB in patients who received SLV.ConclusionsUltrasound-guided SGB improves respiratory mechanics, hemodynamics, and inflammatory responses during SLV. Our findings suggest a protective role of SGB in reducing complications associated with SLV.Clinical Trial RegistrationThe study was registered in the Chinese Clinical Trial Registry (#ChiCTR2200063210).

Addressing lung truncation in 99mTc-MAA SPECT/CT for 90Y microsphere radioembolization treatment planning

BackgroundPrior studies have established that macroaggregated albumin (MAA)-SPECT/CT offers more robust lung shunt fraction (LSF) and lung mean absorbed dose (LMD) estimates in 90Y radioembolization in comparison to planar imaging. However, incomplete SPECT/CT coverage of the lungs is common due to clinical workflows, complicating its potential use for LSF and LMD calculations. In this work, lung truncation in MAA-SPECT/CT was addressed via correction strategies to improve 90Y treatment planning.MethodsLung truncation was simulated in 56 cases with adequate (> 90%, mean: 98%) lung coverage in MAA-SPECT/CT by removing slices in ~ 5 mm increments from the lung apices to the diaphragm. A wide range of lung coverages from 100% to < 1% in ~ 2% increments were created. LSF and LMD were calculated with four methods. (1) 2D planar imaging standard (not truncated), truncated lung SPECT/CT data was: (2) used with no corrections (SPECTTrunc), (3) uniformly extrapolated to full lung coverage (SPECTUniform), (4) fit with an empirical model to predict lung counts at full lung coverage (SPECTFit). To determine counts for LSF, full lung volumes, those modified at the lung/liver boundary (Lungs 2-cm), and those isolated to the left lung (Left Lung) were used. The correction methods were then applied to 31 independent cases without full lung coverage (< 90%, mean: 74%). The variations in LSF and LMD estimates from each correction method were analyzed.ResultsAveraged across simulated lung coverages from 40 to 80%, percent errors relative to non-truncated data for SPECTTrunc were (mean ± σ) − 22% ± 15% for LSF and 34% ± 29% for LMD. SPECTUniform had similar errors with 29% ± 26% for both LSF and LMD. SPECTFit yielded the most accurate and precise estimates for LSF and LMD, with errors of 11% ± 20% for both. The Left Lung approach equalized LMD errors in all three correction methods, with percent errors of 3% ± 17% (SPECTTrunc), 2% ± 17% (SPECTUniform), and 4% ± 13% (SPECTFit). In the 31 cases without ground truth LSF or LMD, Left Lung produced highly comparable LMD estimates, with a mean (max) coefficient of variation across the three correction methods of 4% (20%).ConclusionLSF and LMD can be estimated for 90Y radioembolization using truncated lung coverage data in MAA-SPECT/CT. Empirical models to predict lung counts at full lung coverage produced LSF and LMD estimates with minimal bias and uncertainty. With lung/liver boundary adjustments, all SPECT/CT methods assessed in this work yielded LMD estimates comparable to ground truth, even down to 50% lung coverage.

Survival comparison in adults with congenital systemic to pulmonary shunt and borderline elevated pulmonary vascular resistance versus Eisenmenger syndrome

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) is a consequence of unrepaired large systemic-to-pulmonary shunts. The long-term data of adult patients who have PAH-CHD with elevated pulmonary vascular resistance (PVR) are limited. We aimed to investigate the survival of adults who had PAH-CHD with predominantly left-to-right (L-R) shunts with (1) borderline-to-high PVR and (2) treat-and-repair compared with those with Eisenmenger syndrome (ES). From 1995 to 2021, 99 adults with ES (age 34.1 ± 11.2 years) and 118 adults with PAH-CHD with predominantly L-R shunts (age 39.1 ± 13.7 years) were eligible. The PVR in the ES group was 21.0 ± 13.1 WU. Most ES patients (97%) received pulmonary vasodilator therapy. Among the 118 patients with PAH-CHD with predominantly L-R shunts, the baseline PVR was 7.6 ± 4.6 WU, and 78 patients (66.1%) had borderline to high PVR (≥ 5 WU). In the group, 105 patients (88.9%) underwent repair; 84 had defect closure, and 21 had fenestrated closure. Treat-and-repair was used to treat 53 patients with a preoperative final PVR of 3.58 ± 2.63 WU. No early postoperative deaths were reported. At a median follow-up time of 5.4 years (range 0.1–23.6 years), the 10- and 15-year survival rates of adults with borderline PVR were 82.3% and 82.3%, respectively, which were not inferior to the rates for patients with ES, which were 77.8% and 71.2%, respectively (p = 0.41). The survival rate of patients who underwent treat-and-repair was slightly better than that of patients who underwent ES, although the difference was not statistically significant (p = 0.19). Independent mortality risk factors were functional class III-IV at initial presentation (hazard ratio 5.7, 95% CI 1.2–26.6; p = 0.02) and oxygen saturation < 94% at the most recent visit (hazard ratio 9.4, 95% CI 2.1–42.9; p = 0.004).Trial registration: TCTR20200420004.

Open-lung ventilation versus no ventilation during cardiopulmonary bypass in an innovative animal model of heart transplantation

Open-lung ventilation during cardiopulmonary bypass (CPB) in patients undergoing heart transplantation (HTx) is a potential strategy to mitigate postoperative acute respiratory distress syndrome (ARDS). We utilized an ovine HTx model to investigate whether open-lung ventilation during CPB reduces postoperative lung damage and complications. Eighteen sheep from an ovine HTx model were included, with ventilatory interventions randomly assigned during CPB: the OPENVENT group received low tidal volume (VT) of 3 mL/kg and positive end-expiratory pressure (PEEP) of 8 cm H20, while no ventilation was provided in the NOVENT group as per standard of care. The recipient sheep were monitored for 6 h post-surgery. The primary outcome was histological lung damage, scored at the end of the study. Secondary outcomes included pulmonary shunt, driving pressure, hemodynamics and inflammatory lung infiltration. All animals completed the study. The OPENVENT group showed significantly lower histological lung damage versus the NOVENT group (0.22 vs 0.27, p = 0.042) and lower pulmonary shunt (19.2 vs 32.1%, p = 0.001). In addition, the OPENVENT group exhibited a reduced driving pressure (9.6 cm H2O vs. 12.8 cm H2O, p = 0.039), lower neutrophil (5.25% vs 7.97%, p ≤ 0.001) and macrophage infiltrations (11.1% vs 19.6%, p < 0.001). No significant differences were observed in hemodynamic parameters. In an ovine model of HTx, open-lung ventilation during CPB significantly reduced lung histological injury and inflammatory infiltration. This highlights the value of an open-lung approach during CPB and emphasizes the need for further clinical evidence to decrease risks of lung injury in HTx patients.

99mTc/90Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics

Transarterial radioembolization (TARE) is a well-established clinical therapy for the treatment of patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who are ineligible for radical treatment. However, commercialized radioactive microspheres still have some issues, such as high density, complicated preparation, non-biodegradability. Furthermore, the use of different radioactive microspheres during TARE and lung shunt fraction assessment has led to inconsistencies in biodistribution in certain cases. This study employed biodegradable hyaluronic acid (HA) as the backbone and modified with bisphosphonate and methacrylic acid to prepare biodegradable gel microspheres (HAMS) using the water-in-oil emulsification and photo-crosslinking for labeling the diagnostic radionuclide of 99mTc and therapeutic radionuclide of 90Y. Both 99mTc radiolabeled HAMS (99mTc-HAMS) and radiolabeled 90Y-HAMS (90Y-HAMS) were highly efficient in radiolabeling and exhibited excellent radiostability in vitro and in vivo. 99mTc-HAMS are highly effective in assessing the LSF, while 90Y-HAMS, administered though TARE, are effective in inhibiting the growth of in situ HCC without any side effects. Both 99mTc-HAMS and 90Y-HAMS have promising clinical applications in HCC theranostics.

Echocardiographic Screening of Liver Transplant Candidates-Prevalence of Features of Portopulmonary Hypertension.

Background: The prevalence of portopulmonary hypertension (PoPH) is relatively low; however, its presence significantly worsens patients' prognosis. When diagnosed, PoPH can be effectively treated, and specific therapies can lead to a substantial reduction in pulmonary circulation pressure, facilitating the safe performance of liver transplantation. Echocardiography is recommended as a first-line method for the non-invasive diagnosis of pulmonary hypertension and serves as a valuable screening tool for patients being evaluated for liver transplantation (LT). The objective of this study was to thoroughly assess the occurrence of echocardiographic signs indicative of pulmonary hypertension and hepatopulmonary syndrome (HPS) in candidates for LT. We assumed that our analysis also made it possible to assess how frequently these candidates require further invasive diagnostics for pulmonary hypertension at specialized centers and how often they may need targeted treatment for pulmonary arterioles as a bridge to transplantation, which could improve patient outcomes. Additionally, this study included a comprehensive review of the current literature. Methods: All LT candidates underwent standardized transthoracic echocardiography and contrast evaluation to identify intrapulmonary vascular shunts. Results: A total of 152 liver transplantation candidates (67 women, mean age 50.6 years) were included in the analysis. The estimated echocardiographic probability of pulmonary hypertension was classified as high in only one patient. However, 63 patients exhibited the visualization of microbubbles in the left heart chambers after an average of six cardiac cycles (ranging from three to nine cycles) following their appearance in the right heart. Conclusions: Our analysis shows that the features of PoPH and a high probability of PH were very rare in the LT candidates, and echocardiographic signs suggestive of hepatopulmonary syndrome were more prevalent. Liver transplant candidates need screening for PoPH and HPS, as both PoPH and HPS significantly worsen their prognosis, but specific PH treatment as a bridge to transplantation improves PoPH patients' survival.

Techno-economic assessment and multi-objective optimization of a hybrid methanol-reforming proton exchange membrane fuel cell system with cascading energy utilization

This article proposes an innovative tri-generation system aimed at improving the efficiency of proton exchange membrane fuel cell (PEMFC) combined methanol steam reforming (MSR) setups. The proposed system merges MSR-PEMFC with an organic Rankine cycle (ORC) and Latent-thermal energy storage (LTES) to produce heat, electricity, and purified water concurrently. The MSR process, using methanol and water, acts as a hydrogen source for the PEMFC. Waste heat from the reforming reaction and PEMFC exhaust gases is efficiently recuperated through ORC and LTES. Moreover, a composite phase change material comprising 8 % expanded graphite and 92% industrial paraffin wax is formulated for LTES, exhibiting a thermal conductivity of 4.65 Wm−1K−1. Parametric analysis of the methanol-reforming fuel cell system suggests a methanol to water mass ratio of 1.5 and a pressure swing absorption shunt fraction of 0.77. Multi-objective optimization of the recovery system using the Non-dominated Sorting Genetic Algorithm II algorithm is conducted, with objective functions including tri-generation system exergy efficiency, CO2 emission reduction, and total cost to evaluate system thermodynamic, environmental, and economic performance, respectively. The ORC system employing R245fa and R600 yields 27 % more electricity than the R152a-based system, with exergy efficiencies approximately twice as high. Compared to conventional systems, the proposed tri-generation system achieves an energy efficiency of 81 % and exhibits a 22 % enhancement in energy efficiency.

Abstract 4137845: A single-cell lung atlas of human pulmonary arterial hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: We hypothesis that single-cell RNA sequencing analysis can help understand the cellular and molecular mechanisms that drive the disease initiation and progression. Methods: 10 healthy donors, 10 idiopathic PAH, 10 drug and toxin induced PAH, 10 systemic and pulmonary shunting induced PAH patients from both male and female, and different ethical groups and races, and ages were obtained from PHBI. Lung tissue specimens were processed for fixed scRNA-seq. The cell proportion change, gene expression, and pathway analysis were evaluated between different disease subclasses, sex, age on different cell types. Results: Our analysis reveals 317,414 cells, 33 clusters and 9 major cell types, including endothelial cells (ECs), alveolar cells, fibroblast, smooth muscle cells (SMCs), pericytes, myeloid cells, lymphocytes, airway epithelial cells, platelet. Cell proportion analysis demonstrated an increase in the proportions of venous ECs, adventitial fibroblasts and myofibroblasts, alveolar macrophages, B cells, plasma cells and a reduction in capillary ECs 2 and pericytes in PAH lungs. KEGG Pathway analysis showed that upregulated pathways related Herpes simplex virus 1 infection, ECM-receptor interaction, Complement and coagulation cascades, Hedgehog signaling, TGF-beta signaling pathway, and downregulated pathways related to IL-17 signaling, TNF signaling, MAPK signaling pathway were enriched in the PAH patients. Female PAH patients exhibit an increase of myofibroblasts and platelets proportion compared to male PAH patients. MsigDB Hallmark Pathway analysis showed that p53 pathway was upregulated, whereas Inflammatory Response, Hypoxia, Epithelial Mesenchymal Transition were downregulated in female PAH patients. PAH patients older than 21 years exhibit an increase in the cell proportion of Platelet, SMCs, Arterial ECs and Venous ECs, and alveolar macrophages and a reduction of B cells and plasma cells. Conclusions: Our integrated analysis of human PAH lung atlas dataset provides a comprehensive understanding of lung cell populations and molecular signature in PAH patients with different sex, age and subclasses

Impact of intravenous infusion of lidocaine on intrapulmonary shunt and postoperative cognitive function in patients undergoing one-lung ventilation.

Intravenous infusion of lidocaine as an anesthesia adjuvant can improve patient outcomes, but its impact on intrapulmonary shunt during one-lung ventilation (OLV) has not been clarified. To determine the effect of intravenous lidocaine infusion on intrapulmonary shunt during OLV and postoperative cognitive function in video-assisted thoracoscopic surgery (VATS). Sixty patients who underwent OLV for thoracic surgery were randomized to receive intravenous infusion of lidocaine (lidocaine group, n = 30) or normal saline (control group, n = 30) for anesthesia induction. Arterial and venous blood gases were measured during two-lung ventilation and at 15 and 30 min after OLV (OLV + 15 and OLV + 30). The Mini-Mental State Examination was administered before the surgery and at postoperative 12 months to assess patient cognitive function. No significant difference was found in intrapulmonary shunt fraction (Qs/Qt) between the lidocaine group and the control group at OLV + 15 (p = 0.493) and OLV + 30 (p = 0.754). The lidocaine group used significantly lower doses of propofol and remifentanil compared to the control group (both p < 0.001). Furthermore, no significant difference was observed in the incidence of postoperative cognitive dysfunction between the lidocaine group and the control group at 1 year post-operation (3.3% vs 6.7%, p = 0.554). Intravenous lidocaine administered in VATS had no significant impact on intrapulmonary shunt during OLV or postoperative cognitive function. However, it significantly reduced the doses of anesthetics used during the surgery.

Glenn circulation causes early and progressive shunting in a surgical model of pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformations (PAVMs) universally develop in patients with single ventricle congenital heart disease. Single ventricle PAVMs have been recognized for over 50 years but remain poorly understood. To improve our understanding, we developed a surgical rat model of Glenn circulation and characterized PAVM physiology over multiple time points. We performed a left thoracotomy and end-to-end anastomosis of the left superior vena cava to the left pulmonary artery (unilateral Glenn), or sham surgical control. To assess PAVM physiology, we quantified intrapulmonary shunting using two independent methods (bubble echocardiography and fluorescent microsphere injection). Additionally, we performed arterial blood gas measurements to assess oxygenation and plethysmography to assess ventilation. We identified pathologic intrapulmonary shunting by bubble echocardiography as early as 2 weeks post-Glenn, and shunting continued at 2- and 6-months post-Glenn. Shunting also progressed over time, demonstrated by increased shunting of 10 μm microspheres at 6 months. Shunting was accompanied by mildly decreased oxygenation but no differences in ventilation. Our surgical animal model of unilateral Glenn circulation recreates the clinical condition of single ventricle PAVMs with early and progressive intrapulmonary shunting. This model is poised to characterize single ventricle PAVM pathophysiology and lead to mechanistic and therapeutic discovery.

Abstract 392: Recurrent ischemic strokes in a patient with ITP, case report and literature review

Introduction/Purpose Immune Thrombocytopenic purpura (ITP) is an autoimmune acquired thrombocytopenia caused by autoantibodies against platelet antigens leading to platelet destruction and platelet underproduction. Patients with ITP usually have a higher risk of bleeding compared to the general population, however thrombocytopenia in ITP is not necessarily protective against thrombosis. While the exact pathophysiology of hypercoagulability in ITP is still not fully understood and not enough data in literature guiding stroke management in patients with ITP as the primary stroke risk factor, there are multiple etiologies suggested including inflammation, antiphospholipid antibodies in some patients, or the effects of certain treatments such as glucocorticoids and Thrombopoietin receptor agonists (TPO‐RAs) Methods A single case report, literature review through PubMed Results A 65‐year‐old male with a history of unprovoked deep vein thrombosis (DVT) and pulmonary embolism (PE) while on Rivaroxaban presented with worsening headaches and cognitive dysfunction. A CT scan of the head revealed bilateral subacute frontal lobe infarcts with an embolic appearance. Initial laboratory tests showed thrombocytopenia (54,000), and a hypercoagulable workup, including tests for anticardiolipin antibodies, antiphospholipid antibodies, beta‐2 glycoprotein antibodies, factor V Leiden mutation, and Prothrombin gene mutation, returned negative. A bone marrow biopsy revealed immature megakaryocytes without morphological abnormalities. Transthoracic and transesophageal echocardiograms did not show any intracardiac or intrapulmonary shunts, and telemetry monitoring did not detect any arrhythmias. The patient was switched from Rivaroxaban to Warfarin, with an INR target of 2.0‐3.0, and was started on glucocorticoids and Rituximab. Follow‐up showed an improvement in platelet count. Eight months after discharge, the patient experienced a new right pontine infarct; at that time, his INR was 2.34, and a repeat stroke workup was inconclusive. The Warfarin dose was adjusted to achieve an INR target of 2.5‐3.5. Over a subsequent 4‐year follow‐up period, the patient did not experience any additional strokes. Conclusion Patients with immune thrombocytopenic purpura (ITP) face an increased risk of stroke, often of cryptogenic origin. While thrombocytopenia in ITP is not protective against thrombosis, it certainly increases the risk of bleeding in individuals on anticoagulant therapy, making management more complex. Further research is needed to develop guidelines for managing stroke in ITP patients particularly who lack conventional stroke risk factors Additionally, the potential role of anti‐inflammatory agents, such as glucocorticoids, in reducing stroke risk in this population warrants investigation.

Individualized positive end-expiratory pressure in laparoscopic surgery: a randomized controlled trial.

The reduction in functional residual capacity (FRC) is a significant pathological factor in the development of postoperative pulmonary complications. Appropriate positive end-expiratory pressure (PEEP) is critical to preserve FRC during mechanical ventilation. Our previous study suggests that using driving pressure-guided PEEP can reduce postoperative pulmonary complications. In this study, we hypothesize that individualized PEEP can increase immediate postoperative FRC and improve lung ventilation. This single-centered, randomized controlled trial included a total of 91 patients scheduled for laparoscopic surgery for colorectal carcinoma. Patients were randomly assigned to receive individualized PEEP guided by minimum driving pressure or a fixed PEEP of six cmH<inf>2</inf>O. The primary outcome was postoperative FRC. Secondary outcomes included the incidence of postoperative pulmonary complications, postoperative Oxygenation Index, alveolar-arterial oxygen tension difference (P<inf>A-a</inf>O<inf>2</inf>), intrapulmonary shunt (Q<inf>S</inf>/Q<inf>T</inf>), and Respiratory Index, as well as lung ventilation measured by electrical impedance tomography. The median value of PEEP in the individualized group was 14 cmH<inf>2</inf>O, with an interquartile range of 12-14 cmH<inf>2</inf>O. The postoperative FRC was significantly higher in the individualized PEEP group than that in the PEEP six cmH<inf>2</inf>O group (32.8 [12.8] vs. 25.0 [12.6] mL/kg, P=0.004). Patients receiving driving pressure-guided PEEP also had significantly higher Oxygenation Index, better ventilation distribution, and lower PA-aO<inf>2</inf>, Q<inf>S</inf>/Q<inf>T</inf>, and Respiratory Index. Driving pressure-guided PEEP can preserve postoperative FRC and provide better ventilation and oxygenation for patients undergoing laparoscopic colorectal surgery.

Anesthetic management for aspiration thrombectomy using the Penumbra Indigo System® in pediatric patients with congenital heart disease

ObjectivesDescribe clinical characteristics and outcomes including transfusion requirements of pediatric patients with congenital heart disease undergoing aspiration thrombectomy DesignRetrospective chart review SettingQuaternary academic children's hospital ParticipantsPatients < 18yrs with congenital heart disease undergoing aspiration thrombectomy from November 2017-February 2022. Measurements and main results13 patients underwent mechanical thrombectomy with the Penumbra Indigo System®. Median age was 3.8 years and median weight was 15.2kg. Seven patients had palliated single ventricle and 6 had biventricular circulation. Nine patients were receiving ICU care pre-procedure and 12 required ICU care post-procedure. Indications for thrombectomy included systemic venous thrombus (n=7), pulmonary arterial thrombus (n=3), systemic arterial thrombus (n=2), and systemic to pulmonary shunt occlusion (n=1). Median estimated blood loss was 7.7ml/kg (interquartile range 1.4ml/kg-15.8ml/kg, range 0.5ml/kg-51.5ml/kg). Seven patients required intraoperative transfusion of pRBCs (n=4), FFP (n=2), platelets (n=3), and/or cryoprecipitate (n=1). In those requiring transfusion, median transfusion volume was 22ml/kg (interquartile range 15.5ml/kg-76.5ml/kg, range 9.3ml/kg-132.8ml/kg). Thrombectomy was successful in 8 of 13 patients, although 3 experienced recurrent thrombosis. ConclusionsMechanical aspiration thrombectomy is increasingly used to treat critically ill pediatric patients and presents unique anesthetic considerations particularly related to the need for volume and blood product resuscitation

Combined Norwood and Modified Left-Sided Starnes Procedures for Congenitally Corrected Transposition of the Great Arteries.

The combination of congenitally corrected transposition of the great arteries (ccTGA), Ebstein anomaly of the systemic atrioventricular valve, and critical systemic ventricular outflow tract obstruction is extremely rare. Management of a neonate with these lesions in cardiogenic shock is quite challenging. Tricuspid valve exclusion has been increasingly and successfully used to manage neonatal Ebstein anomaly patients. We extended this idea of tricuspid valve exclusion (modified Starnes) combined with a Norwood Stage 1 operation with a modified systemic to pulmonary artery shunt to successfully manage a neonate with ccTGA, severe systemic atrioventricular valve regurgitation, and critical ventricular outflow tract obstruction.