Circulatory and Respiratory Physiology Commons^™

Using Atrial Pacing Trials After Tavr To Assess Conduction Abnormalities And Predict Need For Pacemaker Implantation, Hemish M. Philip, Matthew R. Summers, Shirish R. Yasa, Hasani Amir, Daiwik P. Munjwani, Thomas A. Cook, Matthew G. Jackson

Cardiovascular Research Symposium

Abstract:

Background: Transcatheter Aortic Valve Replacement (TAVR) is the standard of care for many patients with severe aortic stenosis who cannot undergo surgical intervention. However, conduction disturbances remain a frequent complication, particularly with self-expanding valves. This often leads to permanent pacemaker implantation (PPI). At Sentara Heart Hospital, atrial pacing at 140 bpm is standard practice during TAVR to assess AV conduction.

Objective: This study aims to evaluate whether preserved 1:1 atrioventricular (AV) conduction during routine atrial pacing at 140 bpm after self-expanding TAVR predicts a low likelihood of requiring PPI, thus yielding a high negative predictive value (NPV).

Methods: We …

Development Of Overt Hypo-Attenuated Leaflet Thickening Following Transcatheter Aortic Valve Replacement, Stephonda Lewis, Hemish M. Philip, Matthew Summers

Cardiovascular Research Symposium

Background: Transcatheter aortic valve replacement (TAVR) is a cornerstone therapy for severe aortic stenosis. Up to one-third of patients develop hypoattenuated leaflet thickening (HALT) within the first year post-TAVR. HALT, a form of leaflet thrombosis, can progress to leaflet immobility and structural deterioration. Despite its significance, no unified approach exists for screening or management of HALT after TAVR.

Case Presentation: A 64-year-old woman presented with shortness of breath on exertion. Exam revealed a 3/6 systolic murmur, and echocardiogram confirmed severe aortic stenosis. She underwent TAVR with resolution of symptoms and was discharged on clopidogrel (Plavix) as single antiplatelet therapy. Two …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

A Novel Non-Rodent Animal Model Of Hydrochloric Acid-Induced Acute And Chronic Lung Injury, Pavel A. Solopov, Ruben Manuel Luciano Biancatelli, Tierney Day, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Hydrochloric acid is one of the most prevalent and hazardous chemicals. Accidental spills occur in industrial plants or during transportation. Exposure to HCl can induce severe health impairment, including acute and chronic pulmonary diseases. We have previously described the molecular, structural, and functional aspects of the development of chronic lung injury and pulmonary fibrosis caused by intratracheal instillation of HCl in mice. Although mouse models of human disease have many advantages, rodents are evolutionary far from human and exhibit significant anatomical and physiological differences. Genetic and anatomic similarities between rabbits and humans are significantly higher. Rabbit models of HCl-induced lung …

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV₁, FVC, and FEV₁/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …

The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, Anita Kovacs-Kasa, Boris A. Gorshkov, Kyung-Mi Kim, Sanjiv Kumar, Stephen M. Black, David J. Fulton, Christiana Dimitropoulou, John D. Catravas, Alexander D. Verin

Bioelectrics Publications

The goal of this study was to investigate the role of MLC phosphatase (MLCP) in a LPS model of acute lung injury (ALI). We demonstrate that ectopic expression of a constitutively-active (C/A) MLCP regulatory subunit (MYPT1) attenuates the ability of LPS to increase endothelial (EC) permeability. Down-regulation of MYPT1 exacerbates LPS-induced expression of ICAM1 suggesting an anti-inflammatory role of MLCP. To determine whether MLCP contributes to LPS-induced ALI in vivo, we utilized a nanoparticle DNA delivery method to specifically target lung EC. Expression of a C/A MYPT1 reduced LPS-induced lung inflammation and vascular permeability. Further, increased expression of the …

Hsp90 Inhibition Suppresses Nf-Κb Transcriptional Activation Via Sirt-2 In Human Lung Microvascular Endothelial Cells, Gagan S. Thangjam, Charalampos Birmpas, Nektarios Barabutis, Betsy W. Gregory, Mary Ann Clemens, Joseph R. Newton, David Fulton, John D. Catravas

Bioelectrics Publications

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation …

Longitudinal Association Of Sleep-Disordered Breathing And Nondipping Of Nocturnal Blood Pressure In The Wisconsin Sleep Cohort Study, Khin Mae Hla, Terry Young, Laurel Finn, Paul E. Peppard, Mariana Szklo-Coxe, Maryan Stubbs

Community & Environmental Health Faculty Publications

Study objectives: The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping.

Methods: The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by …