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Salma Fleifil,1 Lyna Azzouz,1 Gina Yu,1 Corey Powell,2 Nikhil Bommakanti,1 Yannis M Paulus1,3 1Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center University of Michigan Medical School, Ann Arbor, MI, USA; 2Department of Statistics, University of Michigan, Ann Arbor, MI, USA; 3Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USACorrespondence: Yannis M Paulus, Department of Ophthalmology and Visual Sciences, Department of Biomedical Engineering, University of Michigan, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI, 48105, USA, Tel +734 764-4182, Fax +734 936-3815, Email ypaulus@med.umich.eduIntroduction: Diabetic retinopathy (DR) is a leading cause of blindness. Retinal imaging is an important tool to monitor the progression of DR. While seven-standard retinal fields are the traditional method for evaluating DR, ultra-widefield (UWF) imaging allows for improved visualization of peripheral areas of nonperfusion (NP) and neovascularization (NV), which could be used as biomarkers to monitor and predict progression of DR.Methods: A retrospective, cross-sectional study was conducted on 651 eyes from 363 patients diagnosed with type 1 or type 2 diabetes who received UWF-FA over 10 years. Fluorescein Angiography (FA) images were segmented, and surface areas of NP and NV were analyzed using multivariate regression to determine if biomarkers of DR and DR severity are associated with increasing areas of NP and NV.Results: Each additional year with a diagnosis of DR was associated with a 10.75 mm2 increase in the total NP (95% CI, 1.94— 19.56; P = 0.02) and 7.87 mm2 increase in NP far-periphery (95% CI, 1.62— 14.13; P = 0.01). A one-unit change in severity as defined by the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification was associated with a 25.75 mm2 increase in total NP (95% CI, 11.16— 40.33; P = 0.001), a 13.15 mm2 increase in mid-periphery NP (95% CI, 6.93— 19.38; P < 0.0001), and a 12.29 mm2 increase in far-periphery NP (95% CI, 3.62— 20.97; P = 0.01).Discussion: Biomarkers identified through UWF imaging such as total and regional areas of NP can be used to monitor and predict the progression of DR. This may provide a quantitative method for prognostication in patients with DR.keywords: diabetic retinopathy, ultra-widefield fluorescein angiography, nonperfusion, neovascularization

Background: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2.Methods: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O2 (FiO2) of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor.Results: During tidal ventilation, the expiratory lung collapse increased when I:E <1 [mean (standard deviation) lung collapse=15.7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001).Conclusions: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury. [ABSTRACT FROM AUTHOR]

Purpose: To perform a time-driven, activity-based cost analysis of retinal detachment (RD) surgery and compare it with reimbursement rates. Methods: This economic analysis at a single academic institution used time-driven, activity-based costing methodology to determine the cost of rhegmatogenous RD repair with primary pars plana vitrectomy. A process flow map was created to highlight each surgical case's operative episodes, including clinical follow-ups. Time logs were obtained from the electronic health record for each operative phase and clinical follow-up. The overhead and anesthesia costs were collected from the institution's cost accounting system. The direct material and personnel costs were obtained from internal financial data. Results: Seventy-six cases that met the inclusion criteria were included in the cost analysis study. The time-driven, activity-based cost of RD was $6247.17, and the reimbursement was $5442.91. Therefore, each procedure had a net negative loss of $804.26. To break even, the average operation time would need to be reduced from the determined average of 90.49 minutes to 64.90 minutes. Conclusions: This study found that Medicare underestimates the true cost of RD surgery. Changes in referral patterns may be motivated by reimbursement rates lower than the cost of the procedure, which could ultimately affect patient access to care., Competing Interests: The authors declared no potential conflicts of interests with respect to research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: To describe a novel case of secondary multiple evanescent white dot syndrome in a patient with North Carolina Macular Dystrophy (NCMD)., Methods: The patient was evaluated with ultra-widefield color and autofluorescence imaging, fluorescein angiography, and spectral-domain optical coherence tomography., Results: A 43-year-old man with longstanding blurred vision in both eyes acutely developed glare in the right eye after an upper respiratory illness. He had chorioretinal atrophy in both eyes consistent with North Carolina Macular Dystrophy, which was later confirmed by genetic testing. He alsyo had white spots in the macula of the right eye consistent with secondary MEWDS. The diagnosis of secondary MEWDS was confirmed with fundus autofluorescence and fluorescein angiography, as well as a negative infectious workup. His symptoms and the retinal lesions had resolved by 11 weeks and after a short course of oral corticosteroids., Conclusion: Prior studies have suggested a link between disruption of the RPE/Bruch's membrane complex and secondary MEWDS. This report describes the first case of secondary MEWDS after NCMD and provides further support for this association.

Purpose: We describe the case of an 80-year-old man with bilateral minocycline-induced retinal pigment epithelium (RPE) hyperpigmentation, which initially masqueraded as AMD. Secondarily, using multimodal imaging features, we propose a mechanism for the development of minocycline-induced RPE hyperpigmentation., Observations: The patient was referred with concern for AMD given the presence of macular drusenoid deposits on optical coherence tomography. However, funduscopic evaluation showed dense granular parafoveal hyperpigmentation, with a diffuse slate-colored hyperpigmentation throughout the peripheral fundus. Short-wavelength fundus autofluorescence of the macula disclosed no irregularities (as would be expected with drusen) while on near-infrared reflectance (NIR) imaging, numerous hyperreflective foci were noted corresponding to the hyperpigmented granules observed clinically (as would instead be seen with melanin deposits). Clinical examination was notable for blue-gray hyperpigmentation of the lower and upper extremities, as well as of the face, periorbital skin, and sclera. Upon further questioning, the patient disclosed daily oral minocycline use for 15 years for acne rosacea, confirming a diagnosis of minocycline-induced hyperpigmentation of the RPE., Conclusions: Multimodal imaging can be useful for differentiating minocycline-induced RPE hyperpigmentation from similar masquerade entities. Timely diagnosis can prevent progressive vision loss., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Inc.)

Objectives: To determine the locations on the 24-2 visual field (VF) testing grid that are most likely to progress in patients with ocular hypertension (OHTN). Based on a structural model of superior and inferior areas of relative vulnerability at the optic disc, we hypothesized that the nasal and paracentral regions are more prone to show a reduction in sensitivity., Methods: Posthoc analysis of data collected in phases 1 and 2 of the Ocular Hypertension Treatment Study (OHTS). A pointwise analysis was applied to determine the progression patterns in the early and delayed treatment groups. Each group's progression rate and frequency were calculated for each of the 52 locations corresponding to the 24-2 VF strategy, using trend- and event-based analyses, respectively., Results: For the event-based analysis, the events were most commonly found in the nasal and paracentral regions. The same regions, with some modest variation, were found to have the fastest rates of progression (ROP) measured with trend analysis. A similar pattern of progression was observed in both the early and delayed treatment groups. The difference in event rates and ROP between the early and delayed treatment groups was also greatest in the nasal and paracentral regions., Conclusions: Development of VF loss in ocular hypertensive eyes appears to be consistent with the vulnerability zones previously described in glaucomatous eyes with established VF loss. Ocular hypotensive treatment likely helps to slow the rate of progression in these regions. This suggests that careful monitoring of these locations may be useful., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration., Design: Multicenter retrospective analysis., Subjects: Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy., Methods: Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with ≥ 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area., Main Outcome Measures: Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models., Results: Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated > 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3 mm 2 /year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm 2 /year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm 2 /year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P < 0.05)., Conclusions: Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Both granulomatous polyangiitis (GPA) and Crohn's disease (CD) can cause orbital inflammation though rarely coincide and can often be differentiated by presenting features and histological findings. Here, we report the clinical and therapeutic course of a 14-year-old White male with binocular diplopia caused by orbital myositis. Imaging and biopsy obtained at presentation revealed necrosis and necrotizing granulomatous vasculitis suspicious for GPA. He subsequently developed gastrointestinal symptoms and terminal ileitis consistent with CD. Orbital symptoms responded well to high-dose steroids and remained quiet on methotrexate maintenance therapy. While clinical history, thorough physical exam, and complete laboratory work-up are essential in the management of pediatric orbital myositis, orbital biopsy can prove critical for diagnosis and suitable treatment strategy.

Purpose: To review eyes with peripapillary and macular retinoschisis without a visible optic pit or advanced glaucomatous optic atrophy, or No Optic Pit Retinoschisis (NOPIR)., Design: Retrospective multicenter case series., Subjects: The study included 11 eyes of 11 patients., Methods: Retrospective study of eyes with macular retinoschisis without a visible optic pit, advanced optic nerve head cupping, or macular leakage on fluorescein angiography., Main Outcome Measures: Visual acuity (VA), retinoschisis resolution, months to resolution, and recurrence of retinoschisis RESULTS: The mean age was 68.1 ± 17.6 years, mean intraocular pressure was 17.4 ± 3.8 mmHg, and the mean spherical equivalent refractive error was -3.1 ± 2.9 diopters. No subject had pathologic myopia. Seven subjects were treated for glaucoma, and 9 subjects had nerve fiber layer defects on OCT. All eyes had retinoschisis in the outer nuclear layer (ONL) in the nasal macula and extending to the edge of the optic disc, and 8 subjects had fovea-involving retinoschisis. Three nonfoveal and 4 fovea-involved eyes were observed, and 4 fovea-involved eyes with vision loss underwent surgery. Surgery involved preoperative juxtapapillary laser followed by vitrectomy and membrane and internal limiting membrane peeling with intraocular gas and face-down position. The mean baseline VA was significantly worse in the surgery group than that in the observation group (P = 0.020). Retinoschisis resolved and vision improved in all surgical cases. The mean resolution time for the surgery group was 2.75 ± 0.96 months, which was shorter than that for the observation group (28.0 ± 21.2 months; P = 0.014). No eye developed recurrence of the retinoschisis after surgery., Conclusions: Peripapillary and macular retinoschisis can develop in eyes without a visible optic pit or advanced glaucomatous cupping. Eyes without foveal involvement and those with foveal involvement but only mild decrease in vision can be observed for spontaneous resolution. If there is persistent foveal involvement with vision loss, surgery can improve vision by resolving the macular retinoschisis. Surgery for fovea-involved macular retinoschisis without a visible optic pit resulted in faster anatomic resolution and better vision recovery., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: This study aimed to determine whether cases of surgical retinal detachment (RD) repair at a tertiary care center from January 1, 2011 to December 31, 2020 increased proportionately to macular surgery cases as a control and to national trends., Patients and Methods: Current Procedural Terminology codes were used to identify cases of primary RD repair (67107, 67108), complex RD repair (67113), pneumatic retinopexy (67110), and vitrectomy with membrane peeling (67041, 67042) at an academic center and in the Part B National Summary Data Files. Numbers of cases and mean case times at the academic center were determined., Results: We identified 5,183 and 948,831 operative cases locally and nationally, respectively. Between 2011 and 2019, the total volume of RD repair at the academic center increased by 118.7%, compared to 23.3% for cases of membrane peeling. In contrast, surgical RD repairs and membrane peelings increased by 26.0% and 6.8% cases nationally. The ratio of RD repairs to membrane peelings from 2011 to 2019 increased from 1.5 to 2.6 locally compared to 0.6 to 0.7 nationally. Complex RD repairs increased more than primary RD repairs locally (129.3% vs 110.9% cases) and less than primary RD repairs nationally (20.6% versus 30.2% cases)., Conclusion: Cases of surgical RD repair increased disproportionately compared to macular surgery at our institution and compared to RD repairs nationwide. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:505-511.] .

Background/objectives: Do the distributions of surface area of non-perfusion (NP) and neovascularization (NV) on ultra-widefield fluorescein angiography (UWF FA) in patients with diabetic retinopathy (DR) differ significantly?, Subjects/methods: Inclusion criteria were patients who had a UWF FA taken for DR at the Kellogg Eye Center from January 2009 to May 2018. Exclusion criteria included previous panretinal photocoagulation and significant media opacity (e.g., vitreous haemorrhage or significant cataract). UWF FAs were manually segmented for surface areas of NP and NV. The total areas per patient were organized in a histogram, and logarithmically binned to test against power law and exponential distributions. Then, a computational model was constructed in Python 3.7 to suggest a mechanistic explanation for the observed distributions., Results: Analysis of areas of NV across 189 images demonstrated a superior fit by the least squares method to a power law distribution (p = 0.014) with an R 2 fit of 0.9672. Areas of NP over 794 images demonstrated a superior fit with an exponential distribution instead (p = 0.011). When the far periphery was excluded, the R 2 fit for the exponential distribution was 0.9618. A computational model following the principles of self-organized criticality (SOC), akin to earthquake and forest fire models, matched these datasets., Conclusions: These distributions inform what useful statistics may be applied to study of these imaging characteristics. Further, the difference in event distribution between NV and NP suggests that the two phenomena are mechanistically distinct. NV may follow SOC, propagating as a catastrophic event in an unpredictable manner., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Diabetic retinopathy is a leading cause of blindness in working-age adults worldwide. Neovascular leakage on fluorescein angiography indicates progression to the proliferative stage of diabetic retinopathy, which is an important distinction that requires timely ophthalmic intervention with laser or intravitreal injection treatment to reduce the risk of severe, permanent vision loss. In this study, we developed a deep learning algorithm to detect neovascular leakage on ultra-widefield fluorescein angiography images obtained from patients with diabetic retinopathy. The algorithm, an ensemble of three convolutional neural networks, was able to accurately classify neovascular leakage and distinguish this disease marker from other angiographic disease features. With additional real-world validation and testing, our algorithm could facilitate identification of neovascular leakage in the clinical setting, allowing timely intervention to reduce the burden of blinding diabetic eye disease., (© 2023. The Author(s).)

Purpose: The purpose of this study was to assess the relationship between the rate of the glaucomatous visual field (VF) worsening and baseline age and baseline VF mean deviation (MD)., Design: This study was a retrospective, multisite cohort., Participants: A total of 84,711 reliable Swedish Interactive Thresholding Algorithm 24-2 VF tests from 8167 eyes from 5644 patients with ≥6 VF tests, ≥5 years of follow-up, baseline age 18 years or above and baseline MD ≥-10 dB, and at least 2 abnormal VF tests were included from the Glaucoma Research Network Database., Methods: The global mean deviation rates (MDRs) and pointwise total deviation rates (TDRs) of VF progression (dB/y) were calculated for each eye using linear regression. The relationships between MDR and baseline age and MD were determined using linear mixed-effects models and logistic regression, with rapid progression defined as an MDR≤-1.0 dB/y. The relationships between TDR and baseline age and baseline MD were determined using linear mixed-effects models., Main Outcome Measures: Coefficients of the regression models., Results: In individual mixed-effects models both baseline age (β=-0.0079 dB/y; P<0.001) and baseline MD (β=0.012/y; P<0.001) were associated with faster progression. All parameters were statistically significant in the full model with both parameters and their interaction (β=0.00065; P=0.0017) as covariates. With logistic regression, each year increase in baseline age increased the odds of belonging to the rapid-progressing group by a factor of 1.033, and each unit increase in baseline MD (less severe visual loss) decreased the odds by a factor of 0.8821. The mean pointwise TDR ranged from -0.21 to -0.55 dB/y, with the most rapid pointwise progression observed in the nasal and paracentral regions of the field., Conclusions: Older age and worse MD at baseline are associated with more rapid VF progression in this large dataset. The effect of age on MDR is influenced by baseline MD severity, supporting the importance of early detection and more aggressive therapy in older patients with worse VF damage. The pointwise rate of VF loss varies across the VF, providing a means for physicians to more effectively monitor progression.

Aims: Increases in hydrostatic pressure results in endothelial hyperpermeability via eNOS-dependent pathways. Ropivacaine is known to inhibit eNOS activation and to attenuate lung injury. Herein, we sought to determine if ropivacaine regulates pressure-induced lung endothelial hyperpermeability., Main Methods: The effects of ropivacaine on lung permeability were assessed in two models of acute hypertension (AH): the isolated perfused lung preparation where acute increases in left atrial pressure model the hemodynamic changes of severe hypertension, and an animal model of AH induced by norepinephrine. In the IPL model, whole lung filtration coefficient (K f ) was used as the index of lung permeability; pulmonary artery pressure (P pa ), pulmonary capillary pressures (P pc ), and zonal characteristics (ZC) were measured to assess the effects of ropivacaine on hemodynamics and their relationship to K f2 /K f1 . In vivo, ropivacaine effects were investigated on indices of pulmonary edema (changes in P a O 2, lung wet-to-dry ratio), changes in plasma volume and nitric oxide (NO) production., Key Findings: Ropivacaine provided robust protection from pressure-dependent barrier failure; it inhibited pressure-induced increases in K f without affecting P pa , P pc or ZC. In vivo, ropivacaine prevented pressure-induced lung edema and associated hyperpermeability as evidence by maintaining P a O 2 , lung wet-to-dry ratio and plasma volume in levels similar to sham rats. Ropivacaine inhibited pressure-induced NO production as evidenced by decreased lung nitro-tyrosine content when compared to hypertensive lungs., Significance: Collectively these data show that ropivacaine inhibits pressure-induced lung endothelial hyperpermeability and suggest that ropivacaine may be a clinically useful agent to prevent endothelial hyperpermeability when pulmonary pressure is acutely increased., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease with limited therapeutic options. Genome and transcriptome analyses have identified signalling pathways and cancer driver genes with implications in patient stratification and targeted therapy. However, these analyses were performed in bulk samples and focused on coding genes, which represent a small fraction of the genome., Design: We developed a computational framework to reconstruct the non-coding transcriptome from cross-sectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome. We validated the results in an independent cohort of paired epithelial and stromal RNA-Seq derived from laser capture microdissected human pancreatic tumours, allowing us to annotate the compartment specificity of their expression. We employed systems and experimental biology approaches to interrogate the function of epithelial long non-coding RNAs (lncRNAs) associated with genetic traits and clinical outcome in PDA., Results: We generated a catalogue of PDA-associated lncRNAs. We showed that lncRNAs define molecular subtypes with biological and clinical significance. We identified lncRNAs in genomic regions with SCNA and single nucleotide polymorphisms associated with lifetime risk of PDA and associated with clinical outcome using genomic and clinical data in PDA. Systems biology and experimental functional analysis of two epithelial lncRNAs ( LINC00673 and FAM83H-AS1 ) suggest they regulate the transcriptional profile of pancreatic tumour samples and PDA cell lines., Conclusions: Our findings indicate that lncRNAs are associated with genetic marks of pancreatic cancer risk, contribute to the transcriptional regulation of neoplastic cells and provide an important resource to design functional studies of lncRNAs in PDA., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome.

Hypercapnic acidosis (HCA) has beneficial effects in experimental models of lung injury by attenuating inflammation and decreasing pulmonary edema. However, HCA increases pulmonary vascular pressure that will increase fluid filtration and worsen edema development. To reconcile these disparate effects, we tested the hypothesis that HCA inhibits endothelial mechanotransduction and protects against pressure-dependent increases in the whole lung filtration coefficient (K f ). Isolated perfused rat lung preparation was used to measure whole lung filtration coefficient (K f ) at two levels of left atrial pressure (P LA  = 7.5 versus 15 cm H 2 O) and at low tidal volume (LV t ) versus standard tidal volume (STV t ) ventilation. The ratio of K f2 /K f1 was used as the index of whole lung permeability. Double occlusion pressure, pulmonary artery pressure, pulmonary capillary pressures, and zonal characteristics (ZC) were measured to assess effects of HCA on hemodynamics and their relationship to K f2 /K f1 . An increase in P LA2 from 7.5 to 15 cm H 2 O resulted in a 4.9-fold increase in K f2 /K f1 during LV t and a 4.8-fold increase during STV t . During LV t , HCA reduced K f2 /K f1 by 2.7-fold and reduced STV t K f2 /K f1 by 5.2-fold. Analysis of pulmonary hemodynamics revealed no significant differences in filtration forces in response to HCA. HCA interferes with lung vascular mechanotransduction and prevents pressure-dependent increases in whole lung filtration coefficient. These results contribute to a further understanding of the lung protective effects of HCA.