,....,...,
`: n O. 1 7: S LI pp 1.
`: Oct. 26)
`in Health Sci Library
`it Period i ca 1 s
`
`Liquidia's Exhibit 1096
`Page 1
`
`

`

`Supplement to
`Circulation Volume 110 Number 17 October 26, 2004
`
`Abstracts From Scientific Sessions 2004
`Morial Convention Center
`New Orleans, iouisiana
`November 7-10, 2004
`
`UNIV!:FiSliY OF CALIFORNIA
`DAVIS
`NOV 1 7 2004
`
`HEAL TH SCIENCES LIBRARY
`
`Named and Invited Lectures
`2004 Russell Ross Memorial Lectureship in Vascular Biology
`Garret A. FitzGerald, MD . ......... . ... .... . .. ......... ... ..... ................... . ....... .... .. III-A
`
`2004 George Lyman Duff Memorial Lecture
`Henry N. Ginsberg, MD ....... ...... ..... . .. .................... . ...... . ... .. ........ . .......... III-A
`
`2004 Sol Sherry Distinguished Lecture in Thrombosis
`Denisa D. Wagner, PhD .. ............ .. .. . .. ............. .. ................ . .. . ...... . ......... III-A
`
`=:::.,:: ;:wn PA.~.n~ ~ecture ... ... .... .... ............. .... .. .. .... .... ... G III-B
`
`2004 Thomas W. Smith Memorial Lecture
`
`David A. Kass, MD, FAHA .... . ............ ....... ............ . .. .. .. ..... . .. ......... ....... ... III-B
`
`2004 Dickinson W. Richards Memorial Lecture
`Kenneth Weir, MD, FAHA ... . ............... ...... .. .. ........ . ..... ......... ................. .. III-C
`
`2004 Katharine A. Lem bright A ward
`Diane M. Becker, RN, MPH, ScD, FAHA
`
`.... ............ . ... . ....... .... . .. ..... . ............ . . . .. III-C
`
`2004 William W. L. Glenn Lecture
`Timothy Gardner, MD ....... .. .. . .......... . .. ... . ... . . . . ..... . ......... ........ .. . ... . ........ III-C
`2004 William J. Rashkind Memorial Lecture
`Betsy Dresser, PhD .................... . . .. .. . . ... .. . . . .. . ... . ...... . ... ...... ........ . ... . .... III-D
`
`2004 T. Duckett Jones Memorial Lecture
`Jane W. Newburger, MD, MPH ......... ...... . ... . ... . .. ..... ...... , .... ....... .... ......... . ... III-D
`
`2004 Charles T. Dotter Memorial Lecture
`Lewis Wexler, MD .. ....... . ........ ........ . ... . ... . .. . ........... .. .... .. . ... .. .. ... . ........ III-D
`2004 Laennec Society Lecture
`Nanette K. Wenger, MD, FAHA
`
`.. . ..... ....... . ... ......... .. ... .. ... .. . .... ... . ... . . .. .. .. . . ... . III-E
`
`2004 Ancel Keys Lecture
`Darwin R. Labarthe, MD, MPH, PhD ............ .. . ... . ... . .. .......... . . . . . ...... . ..... .. .. . ... . III-E
`
`Note: Abstract numbers are arranged to coincide with abstract titles in the American Heart Association's Scientific Sessions 2002 Program.
`
`Subject and author indexes are keyed to abstract numbers. Authors of all Named and Invited Lectures and New and Young Investigator
`Award/Prize Abstracts are presented in the expanded Table of Contents within this Abstracts issue. Indexes are located at the back of this issue.
`All other supplements to this volume of Circulation will be indexed in the last December issue.
`
`CIRCULATION (ISSN 0009-7322) is published weekly except combined the first two weeks in January and the last two weeks in December by Lippincott Williams & Wilkins at 16522
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`and additional mailing offices. POSTMASTER: Send address changes to CIRCULATION , American Heart Association, Lippincott Williams & Wilkins, 16522 Hunters Green Parkway,
`Hagerstown, MD 21740.
`
`Liquidia's Exhibit 1096
`Page 2
`
`

`

`2004 Lewis K. Dahl Memorial Lecture
`Rhian M. Touyz MD, PhD .... .... ........... .... ...................................... ... ....... 111-F
`2004 Robert I. Levy Endowed Lecture in Lipid Metabolism
`Ronald M. Krauss, MD, FAHA ... ... .... . . . ...................................................... 111-F
`
`New and Young Investigator Award/Prize Abstract Finalists
`Lewis N. and Arnold M. Katz Basic Science Research Prize for Young Investigators
`Karl-Ludwig Laugwitz, Alessandra Moretti, Jason Lam, Peter Gruber, Yinhong Chen, Sarah Woodard, Lizhu
`Lin, Chen-Leng Cai, Michael Reth, Sylvia Evans, Kenneth R. Chien . .. ............................... . .. 111-G
`Patrick Most, Mirko Voelkers, Sven T. Pleger, Erhe Gao, Melanie Boerries, Andrew Remppis, Hugo A. Katus,
`Walter J. Koch ................................................................................ 111-G
`Sathyamangla V. Naga Prasad, Aruni Jayatilleke, Howard A. Rockman .... . ... ... . .... . . . ... ............ 111-H
`Da-Zhi Wang, Dongsun Cao, Zhigao Wang, Shijie Li, Eric N. Olson ...... .... .. .. ...... .... .. .... .. ... . 111-H
`Min Xie, Sam C. Wang, Dou Zhang, Arun J.C. Prahash, Hidemasa Oh, Motoaki Sano, Xiaozhen Wang, Jennifer
`S. Pocius, George E. Taffet, Lloyd H. Michael, Tse-Hua Tan, Mark L. Entman, Michael D. Schneider . .... .. . . ill-H
`Melvin L. Marcus Young Investigator Awards in Cardiovascular Science
`Roselle Abraham, Peter Lim, Charles A. Henrikson, Roland Emokpae, Ronald Li, Leslie Tung, Eduardo Marban .. .. 111-1
`Garvan C. Kane, Atta Behfar, D. Fearghas O 'Cochlain, Roy B. Dyer, Xiao-Ke Liu, Denice M. Hodgson,
`Santiago Reyes, Takashi Miki, Susumu Seino, Andre Terzic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-1
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-1
`Ryoji Koshida, Petra Rocic, Shuichi Saito, William M. Chilian
`Gangjian Qin, Masaaki Ii, Andrea Wecker, Evelyn Bord, Hong Ma, David A. Goukassian, Yung-sup Yoon, Raj
`Kishore, Yan Zhu, Douglas W. Losordo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-J
`. . .................. . 111-J
`Yao Liang Tang, Yi Tang, Keping Qian, Y. Clare Zhang, Leping Shen, M. Ian Phillips
`Subodh Verma, Chao-Hung Wang, William Stanford, Shu-Hong Li, Richard D. Weisel . . . . . . . . . . . . . . . . . . . . . . 111-J
`Cournand and Comroe Young Investigators Prizes in Cardiopulmonary and Critical Care
`Kimberly A. Boddicker, Yi Zhang, Loyd R. Davies, Richard E. Kerber .... : ....... ... .............. .. . .. . 111-K
`Sebastien Bonnet, M. Evangelos D. Michelakis, Sean McMurtry, Gwyneth Harry, Sandra Bonnet, Alois Haromy,
`Stephen L. Archer .............................................................................. 111-K
`Pietro Caironi, Fumito Ichinose, Rong Liu, Rosemary C. Jones, Kenneth D. Bloch, Warren M. Zapol ... . ..... 111-L
`Junyan Gu, Deyanira Prastein, Charles White, Jeffrey Manchio, Richard N. Pierson, Bartley P. Griffith, Paul
`Gurbel, Udaya Tandry, Robert Poston ... .... .. ..... .......... .. ........ . ..... ... .................. 111-L
`Christopher J. Mingone, Sachin A. Gupte, Noorjahan Ali, Richard A. Oeckler, Susan C. Olson, Michael S. Wolin .... 111-L
`Outstanding Research A ward in Pediatric Cardiology
`Brian Feingold, Seda Selamet, Sang C. Park, Beth F. Printz, C. Becket Mahnke, Shing Lee, Charles S.
`Kleinman, -Donna M. Timchak, William H. Neches, Welton M. Gersony ............ . ..................... 111-M
`Marco Stramba-Badiale, Karine Goulene, Giuliano Rosi, Roberta Bini, Silvia G: Priori, Raffaella Bloise, Lia
`Crotti, Patrizia Salice, Vlasta Fesslova, Savina Mannarino, Giuseppe Latini, Roberto Giorgetti, Peter J. Schwartz ........ 111-M
`Wayne Tworetzky, Audrey C. Marshall, Laura B. Myers, Lisa J. Bergersen, Russell T. Jennings, Carol B.
`-Benson, Louise E. Wilkins-Haug, James E. Lock .................. ' ........................... ....... . Iil-N
`Melvin Judkins Young Investigator Award in Cardiovascular Radiology
`Fabao Gao, Bensheng Qiu, Sourav Kar, Xiangcan Zhan, Lawrence V. Hofmann, Xiaoming Yang .... .- ........ 111-N
`. .. .. .. .. 111-0
`C. Javidan-Nejad, D.C. Lesniak, G.S. Chrysant, J. Zheng, R.J. Gropler, T.K. Pi/gram, P.K. Woodard
`Saman Nazarian, David A. Bluemke, Albert C. Lardo, Menekhem M. Zviman, Katherine C. Wu, Stanley Watkins,
`Clerio Azevedo, Timm L. Dickfeld, Glenn R. Meininger, Ronald D. Berger, Hugh Calkins, Joao A. Lima, Henry
`R. Halperin ....... .... ............. ..... ........ .......... ........ ...... ....... .. ............. ill-0
`Monvadi B. Srichai, Che/if Junor, L. Leonardo Rodriguez, Arthur E. Stillman, Richard A. Grimm, Michael L.
`. ......... ....... .. .. . ..... · ............ 111-0
`Lieber, Joan A. Weaver, Nicholas G. Smedira, Richard D. White
`Vivian Thomas Young Investigator Award
`Sydney L. Gaynor, Hersh S. Maniar, Jeffrey B. Bloch, Paul Steendijk, Marc R. Moon ........ . ......... .... 111-P
`Faraz Kerendi, Michael E. Halkos, Hajime Kin, Joel S. Corvera, Daniel J. Brat, Mary B. Wagner, Jakob
`Vinten-Johansen, Zhi-Qing Zhao, Joseph M. Forbess, Kirk R. Kanter, Paul M. Kirshbom ... . .... ........... 111-P
`Paul V. Kochupura, Evren U. Azeloglu, Damon J. Kelly, Sergey V. Doronin, Stephen F. Badylak, Irvin B.
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-P
`Krukenkamp, Ira S. Cohen, Glenn R. Gaudette
`Stephen Kolakowski Jr, Mark F. Berry, Todd Grand, Omar Fisher, M. Astrid Moise, Jeffrey Cohen, Vivian Hsu,
`Y. Joseph Woo ...................... ......... .... .............. .... ......... .... .............. ill-Q
`Frank Langer, Filiberto Rodriguez, Saskia Ortiz, Allen Cheng, Mary K. Zasio, David Liang, George T.
`Daughters, Neil B. Ingels, D. Craig Miller ........ ........... ........................... ... .. .. . . .. 111-Q
`Pierre Voisine, Jian Li, Cesario Bianchi, Tanveer A. Khan, Marc Ruel, Shu-Hua Xu, Jun Feng, Audrey
`Rosinberg, Tamer Malik, Yasunari Nakai, Frank W. Sellke ...................................... ... ... 111-R
`
`Liquidia's Exhibit 1096
`Page 3
`
`

`

`Martha N. Hill New Investigator Awards
`Wen-Wen Li, Anita L. Stewart, Nancy Stotts, Erika S. Froelicher ...... .......... ... . ... ... ............. 111-R
`Philip Moons, Kristien Van Deyk, Kristel Marquet, Els Raes, Leentje De Bleser, Sabina De Geest, Werner Budts . . .. 111-R
`Lorraine S. Evangelista, Kathleen Dracup, Lynn Doering, Debra K. Moser, Jon Kobashigawa ......... . ..... 111-S
`Elizabeth Barrett-Connor Research A ward in Epidemiology and Prevention for Investigators in Training
`Matthew Allison, Michael Criqui, Elena Ho, Julie Denenberg ..... ....... . .. ... .. . ............. . ... . ... 111-T
`Khawaja Afzal Ammar, Steven J. Jacobsen, Richard J. Rodeheffer ........... .. . ... . ... . ...... ..... .. . .. 111-T
`Apoor S. Gami, Daniel E. Howard, Eric J. Olson, Virend K. Somers ............ ............. ..... ...... 111-T
`Frederick A. Masoudi, Charles Baillie, Yongfei Wang, Edward P. Havranek, JoA'nne Micale Foody, John F.
`Steiner, Harlan M. Krumholz .... . .. .. ............... .................. .. ... ............. .... . . .. 111-U
`Nona Sotoodehnia, D~vid Siscovick, Matteo Vatta, Bruce Psaty, Russell Tracy, Jeffrey Towbin, Rozenn Lemaitre,
`Thomas Rea, Peter Durda, Joel Chang, Thomas Lumley, Lewis Kuller, Greg Burke, Susan Heckbert .... . . .. .. 111-U
`Tianying Wu, Susan E. Hankinson, Walter C. Willett, Edward Giovannucci ..... . .. .. .. .............. . .. . . 111-V
`Samuel A. Levine Young Clinical Investigator Awards
`Michaela Scheuermann-Freestone, Damian Tyler, George K. Radda, Stefan Neubauer, Kieran Clarke ... .... .. 111-W
`Michelle M. Kittleson, Shui Q. Ye, Rafael A. Irizarry, John V. Conte, Giovanni Parmigiani, Leslie W. Miller,
`. .......... ............ . . ..... ... . .... 111-W
`Yingjie Chen, Jennifer L. Hall, Joe G.N. Garcia, Joshua M. Hare
`Hidenobu Koga, Seigo Sugiyama, Kiyotaka Kugiyama, Keisuke Watanabe, Hironobu Fukushima, Tomoko
`Tanaka, Tomohiro Sakamoto, Michihiro Yoshimura, Hideaki Jinnouchi, Hisao Ogawa ....... . .. .. .. . ....... 111-W
`Francesca Nesta, Maire Leyne, Charles Simpson, Daisy Dai, Jane E. Marshall, Chaim Yosefy, Judy Hung, Susan
`A. Slaugenhaupt, Robert A. Levine .. . : ... .. ............... ... . ............. ... . .. . ......... ...... . 111-X
`Khim Leng Tong, Sanjiv Kaul, Xin-Qun Wang, Diana Rinkevich, Saul Kalvaitis, Todd Belcik, Wolfgang Lepper,
`William A. Foster, Kevin Wei .. ...... . .. ...... . . .. ......... . ......... ......... . .. ... . . ... ... . . • .. . 111-X
`Laennec Society Young Clinician A ward
`. .. . . . .... . ... ............. . ..... 111-Y
`Marcus Y. Chen, William A. Baker, Bryan R. Haugen, Robert A. Quaife
`. .. .. ........ .. . ... . . ... . .. . .. .......... . . . . . ..... 111-Y
`Andrew C. Lee, Elyse Foster, Yerem Yeghiazarians
`Molly Ware, Eric Awtry, Michael Klein, Thomas Ryan ..... . . .. . ............. . . . .. ... ....... . ... . ..... 111-Y
`NPAM New Investigator Award
`M. Robinson, M. Scheuermann-Freestone, P. Leeson, K. Clarke, S. Neubauer, F. Wiesmann .. . ... . ... . . . .... 111-Z
`
`Abstracts From the Scientific Sessions 2004 . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-1
`
`Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111-837
`
`Subject Index
`
`. . . . . . . . . . . . . . . . . 111-893
`
`Abstracts From the Resuscitation Science Symposium
`
`. . . . . . . . . . . . . . . . . 111-1095
`
`American Heart Association Embargo Policy for Scientific Sessions Abstracts
`
`Abstracts, lectures, and other presentations included in the Scientific Sessions 2004 Supplement published in the
`Oct. 26 issue of Circulation: Journal of the American Heart Association are embargoed for release at the time of
`presentation at the American Heart Association' s Scientific Sessions 2004 (Nov. 7-10) and information may not
`be released before then. Presentation times are listed in the Scientific Sessions 2004 Final Program.
`
`Liquidia's Exhibit 1096
`Page 4
`
`

`

`Supplement to
`Circulation
`
`Abstracts From Scientific Sessions 2004
`
`Committee on Scientific Sessions Program
`The American Heart Association is most grateful to members of the Committee on Scientific Sessions
`Program for their continued dedication and leadership throughout the year in planning the program.
`
`Raymond J Gibbons, Chairman
`Timothy Gardner, Vice Chairman
`
`Council Representatives
`Donna Arnett, Functional Genomics and Translational Biology Interdisciplinary Working Group
`Kenneth Bloch, Cardiopulmonary Perioperative and Critical Care
`Roberto Balli, Member-at-Large
`Lawrence Brass, Stroke Council
`Blase A. Carabello, Clinical Cardiology
`Arlene Chapman, Kidney in Cardiovascular Disease
`Mark A. Creager, Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group
`Alan Daugherty, Arteriosclerosis, Thrombosis, and Vascular Biology
`Christi Deaton, Cardiovascular Nursing
`David D. Gutterman, Basic Cardiovascular Sciences
`David M. Herrington, Epidemiology and Prevention
`Mariel! Jessup, Member-at-Large
`Alan Kadish, Member-at-Large
`John Kugler, Cardiovascular Disease in the Young
`Bruce Lerman, American College of Cardiology, Liaison
`George A. Mensah, Member-at-Large
`Richard C. Pasternak,* Member-at-Large
`Robert C. Robbins, Cardiovascular Surgery and Anesthesia
`David Robertson, High Blood Pressure Research
`Beatriz Rodriguez, Nutrition, Physical Activity, and Metabolism
`Arthur Stillman, Cardiovascular Radiology and Intervention
`Robert Talbert, Member-at-Large
`Gordon F. Tomaselli, Basic Cardiovascular Sciences
`William S Weintraub, Quality of Care and Outcomes Research Interdisciplinary Working Group
`William Wijns, European Society of Cardiology, Liaison
`
`Alice K. Jacobs, President
`Augustus 0. Grant, Immediate Past President
`Rose Marie Robertson, Chief Science Officer
`
`American Heart Association
`
`*Former member
`
`Liquidia's Exhibit 1096
`Page 5
`
`

`

`Supplements to Circulation Published in 2004
`
`Supplements to Circulation are published occasionally and for archival purposes may be bound
`with the regular issue. Supplement page numbers are preceded by a Roman numeral and a
`hyphen. Supplements are indexed with the regular issue with the exception of the Abstracts issue,
`which is indexed within that issue.
`
`Diagnosis of Venous Thromboembolism Supplement
`Gregory L. Moneta, MD, Guest Editor
`Volume 109, Issue 12. March 30, 2004. Pages 1-1-1-27.
`
`Vascular Effects of Statins
`Peter Libby, MD, Guest Editor
`Volume 109, Issue 21. June 1, 2004. Pages 11-1-11-48.
`
`Atherosclerosis: Evolving Vascular Biology and Clinical Implications
`Antonio M. Gotto, Jr, MD, DPhil, Guest Editor
`Volume 109, Issue 23. June 15, 2004. Pages 111-1-111-57.
`
`Markers of Malign Across the Cardiovascular Continuum: Interpretation and Application
`Victor J. Dzau, Guest Editor
`Volume 109, Issue 25. June 29, 2004. Pages IV-1-IV-58.
`
`Treatment of Venous Thromboembolism
`Jeffrey I. Weitz, MD, Guest Editor
`Volume 110, Issue 9. August 31, 2004. Pages 1-1-1-34.
`
`Cardiovascular Surgery Supplement 2004
`Robert C. Robbins, MD, Guest Editor
`Volume 110, Issue 14. September 14, 2004. Pages 11-1-11-286.
`
`Abstracts From Scientific Sessions 2004
`Volume 110, Issue 17. October 26, 2004. Pages 111-1-111-1102.
`
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`
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`Liquidia's Exhibit 1096
`Page 6
`
`

`

`Basic Science
`
`Abstracts From Scientific Sessions 2004
`
`111-295
`
`of membranous RhoA and phosphorylated ERM in brainstem were greater both in angiotensin
`II-treated rats and SHR than in W'r<:f. Valsartan reduced the expression levels of membranous
`'RhoA in angiotensin II-treated rats and SHR. In addition, Y-27632 or valsartan reduced the
`expression levels of phosphorylated 'ERM in both groups. Subcutaneous infusion of phenyl(cid:173)
`ephrine increased SBP to the same level of angiotensin II infusion in W'r<:f. However, it did not
`alter the expression levels of membranous RhoA and phosphorylated ERM. Conclusions: These
`results suggest that 1) the pressor response induced by central infusion of angiotensin II is
`substantially mediated by activation of Rho/Rho-kinase pathway in brainstem via AT1
`receptors, 2) this pathway may also be involved in hypertensive mechanism in SHR.
`
`Endothelial Nitric Oxide and Hypertension in Autonomic Failure
`
`1412
`
`Alfredo Gamboa, Cyndya Shibao, Andre Diedrich, Bonnie K Black, Ginnie Farley, Salish R
`Raj, David-Robertson, ltalo Biaggioni; Vanderbilt Univ, Nashville, TN
`
`More than hatt of patients with autonomic failure (AF) have severe supine hypertension despite
`low or unresponsive norepinephrine levels and often undetectable plasma renin activity. Supine
`hypertension is related to increased vascular resistance but the mechanism is not known. To
`test the hypothesis that nitric oxide deficiency contributes to supine hypertension we blocked
`endogenous nitric oxide synthase with L-NMMA in 5 AF patients and 7 normal controls (supine
`SBP 173:!:6 and 107:!:5 mmHg, respectively). Systolic blood pressure (SBP) was normalized
`to 11 o mmHg in AF with graded head-up tilt, and baroreflexes were eliminated with
`trimethaphan in normal controls to mimic autonomic failure. The presser response to graded
`doses of L-NMMA was shifted to the left in AF (Figure); The dose necessary to increase SBP
`by 30 mmHg was 3.4-fold lower in AF compared to controls (136:!:24 and 465:t103 µ.g/k/min
`respectively, p< 0.02). In conclusion, contrary to our original hypothesis, our results suggest an
`increased tonic release of nitric oxide in AF. Thus, NO deficiency does not contribute to supine
`hypertension in autonomic failure . On the contrary, this enhanced tonic NO may contribute to
`orthostatic hypotension in these patients.
`
`50
`
`40
`
`130
`
`la 20
`~ 10
`
`0
`
`L-NMMA dose (µ/k/mln)
`
`1413
`Oral Administration of a Mineralocorticoid Receptor Antagonist Reduces
`Brain, Heart, and Blood-borne Proinflammatory Cytokines in Heart Failure
`
`Yu-Ming Kang, Carver College of Med, Univ of Iowa, Iowa City, IA; Ralph F Johnson, Univ of
`Iowa, Iowa City, IA; Zhi-Hua Zhang, Carver College of Med, Univ of Iowa, Iowa City, IA;
`Robert M Weiss, Carver College of Med, Univ of Iowa and VA Med Ctr, Iowa City, IA; Alan K
`Johnson, Univ of Iowa, Iowa City, IA; Robert B Felder; Carver College of Med, Univ of Iowa
`and VA Med Ctr, Iowa City, IA
`
`Introduction: Brain and blood-borne cytokines may contribute to neurohumoral excitation in
`heart failure (HF). We previously reported that blockade of mineralocorticoid receptors (MR) in
`the central nervous system with spironolactone (SL) reduces circulating tumor necrosis factor
`[fNF)-a in HF rats. The effect of SL on proinflammatory cytokines (PIC) in the brain and on
`other important circulating PIC - interleukin (IL)-1 fJ and IL-6 - was not determined. Hypothesis:
`Chronic treatment with oral SL will reduce brain and blood-borne PIC in rats with HF following
`Ml. Methods and Results: Rats underwent coronary artery ligation to induce Ml (48.2:t2.0%
`of left ventricle, with ejection fraction of 35.5:!:4.1% by echocardiography), or sham surgery
`(SHAM). Six weeks later, immunohistochemistry of the paraventricular nucleus (PVN) of
`hypothalamus, a region critical to cardiovascular regulation, revealed more PVN neurons (Ml vs
`SHAM, **P< 0.01 ) positive for TNF-a (59.5:!:3.3** vs 10.8:t 0.9) and IL-1fJ (70.7:!:3.9** vs
`13.8:!: 1.2) in Ml (n = 6) than in SHAM (n=6) rats. Double staining demonstrated that these
`neurons were distributed among PVN neurons expressing Fra-like immunoreactivity, indicating
`chronic neuronal activation. Ml rats (n=6) treated with SL (1 mg/kg/day orally for 6 weeks) had
`fewer (Ml + SL vs Ml, #P< 0.01 ) Fra-like posttive PVN neurons (85.5:!:5.4# vs 183.8:!:5.0), and
`fewer PVN neurons positive for TNF-a (22.4:!: 1 .8%# vs 32.4:!:1 .7%) and IL-1 fJ (19.1 :t1 .3%#
`vs 38.4:!: 2.1 %). Levels ofTNF-a, IL-1 fJ and IL-6 in brain and heart tissues and in plasma were
`also lower in Ml rats treated with SL (see table). Conclusion: In rats with ischemia-induced
`heart failure, orally administered SL has a global inhibitory influence on the appearance of
`proinflammatory cytokines in brain, heart and plasma. The beneficial influence of MR
`antagonism in patients with HF may result at least in part from blocking aldosterone-induced
`cytokine synthesis. (Table: *P< 0.05 Ml + SL VS Ml + VEH)
`
`plasma
`IL-6
`(pg/mO
`
`heart IL•
`1,6
`(pg/mg
`protein)
`
`hypotha-
`lamus
`IL-1,6
`(pg/mg
`protein)
`
`hypotha•
`lamus
`TNF·a
`(pg/mg
`protein)
`
`brain-
`stem
`TNF·a
`(pg/mg
`protein)
`
`brain-
`stem
`IL-6
`(pg/mg
`protein)
`
`cortex
`IL-1tl
`(pg/mg
`protein)
`
`heart/
`BW
`Ratio
`(mg/g)
`
`lung/BW
`Ralio
`(mglg)
`
`Group
`
`p1a$ma IL•
`1,6 (pg/mO
`
`Ml + VEH
`
`131 .1::!: 10.9 119.5::!:9.7
`
`53.4::!:6.5
`
`47.U:7.9
`
`6.8: 0.7
`
`6.1 !: 0.9
`
`67.1:::1 0. 1 26.4 :::4.1
`
`7.2 =.0.2
`
`13.5:!:0.6
`
`57.5 ::!:3.1·
`
`53.J = e.s·
`
`32.6:!:5.9. 29.4:!:5. 1· 3.8 =o.e· 2.8 =0.s-
`
`39.4:!: 5.5"
`
`25.8::: 5.2 e.4:::o.3' 12.1 :::o.6·
`
`48.2:!:3.6
`
`33.7:!:2.8
`
`23.7:::6.5
`
`17.4:::4.8
`
`2.8:!: 0.7
`
`2.1 :::0.6
`
`25.3 =.4.8
`
`24.3 =.4.9
`
`3.3=.0.1
`
`5.2 :!:0.3
`
`53.9 =.2.4
`
`36.1 :!: 2.6
`
`27.6:::5.4
`
`18.8 =.4.0
`
`3.2:!: 0.9
`
`2.4 :!: 0.8
`
`28.0:!: 8.7
`
`23.6:!: 6.5
`
`3.4:!: 0.1
`
`5.1 :::0.3
`
`Ml + SL
`(n • 7)
`
`SHAM + Sl
`(n "' 6)
`SHAM+
`VEH
`(n • 6)
`
`Pulmonary Arterial Hypertension: New
`Therapies
`Subspecialty: Integrative Biology
`Wednesday
`Ernest N Moria/ Convention Center, Hall 12
`Abstracts 1414-1418
`
`Inhaled Treprostinil Sodium (TRE) For the Treatment of Pulmonary
`Hypertension
`
`1414
`
`Robert Voswinckel, Beale Enke, Andre Kreckel, Frank Reichenberger, Stefanie Krick,
`Henning Gall, Tobias Gessler, Thomas Schmehl, Markus G Kohstall, Friedrich Grimminger,
`Hossein A Ghofrani, Werner Seeger, Horst Olschewski; Univ Hosp Giessen, Giessen,
`Germany
`,
`
`Objective: To evaluate the effects of inhaled TRE on pulmonary hemodynamics and gas
`exchange in severe pulmonary hypertension (PH) and to assess safety, tolerability and clinical
`efficacy in patients with severe PH. Background: TRE is a stable prostacyclin analogue that has
`been approved for treatment of pulmonary arterial hypertension as a continuous subcutaneous
`infusion. lloprost, another prostacyclin analogue, has been shown to be efficacious in a
`randomised controlled study as repetitive inhalation. Methods: In an open-label study a
`preservative free solution of inhaled TRE was applied to 17 patients with severe pulmonary
`hypertension during Swan-Ganz catheter investigation. Patients received a TRE inhalation by
`use of the pulsed OptiNeb® ultrasound nebulizer (3 single breaths, TRE solution 600 µ.g/ml).
`Hemodynamics were observed for 2 hours. Two patients with idiopathic PAH received
`compassionate treatment with 4 inhalations of TRE per day after the acute test. Results:
`Patients (male/female= 4/13) suffered from iPAH (n = 5), PAH other (n = 8) and CTEPH (n = 4);
`PVR 948 :t 112 dyn•s•cm·•, PAP 48.3 :t 2.7 mmHg, PAWP 8.9 :t 0.5 mmHg, CVP 10.8 :t 1.6
`mmHg, CO 3.8 :t 0.3 I/min, Sv02 61 .8 :t 1.8 %. TRE inhalation resulted in a sustained, highly
`pulmonary selective vasodilatation over 120 minutes. Maximum PVR decrease was -31.2 :t 4.5
`% after 30 min. PVR and SVR at 120 minutes after inhalation were 89.2 :t 4.2 % and 101 .o :t
`4.0 % of the baseline values, respectively. The AUC for the observation period (120min) was
`-22.9 :t 3.8 % for PVR and -4.9 :t 3.2% for SVR. The compassionate use patients have been
`treated for more than 3 months. In both patients NYHA class improved (from IV to Ill and from
`Ill to II), and six minute walk increased (from O m (bedridden) to 143 m, and from 310 m to
`486 m, respectively). No side effects have been observed by the patients during long-term
`treatment. Conclusion: Inhaled TRE shows strong pulmonary selective vasodilatory efficacy
`with a long duration of effect following single acute dosing. TolEi'rability is excellent even at high
`drug concentrations and short inhalation times (3 breaths). Long-term treatment effects are
`very promising. The current results warrant controlled studies investigating this approach in a
`larger series of patients. Supported by Lung RX
`
`Rho-kinase in Pulmonary Hypertension
`
`1415
`
`Ken lshikura, Norikazu Yamada, Akihiro Tsuji, Satoshi Ota, Mashio Nakamura, Masaaki Ito,
`Naoki lsaka, Takeshi Nakano; Mie Univ Sch of Med, Tsu, Japan
`
`Objectives: Pulmonary hypertension (PH) is a poor prognostic disease with limited treatment.
`Rho-kinase is involved in the pathophysiology of several diseases underlying smooth muscle
`hypercontraction. But the role of is unknown. The purpose of this preliminary report was to
`indicate the efficacy of fasudil, a Rho-kinase inhibitor in patients with pulmonary hypertension
`using interventional hemodynamic assessment. Methods: Fasudil was intravenously injected in
`10 patients (9 female, mean :t SD, 46 :t 15 years, NYHA II n= 2, Ill n= 7, IV n= 1) with primary
`(n= 5) and secondary (n=5) PH who were not received any vasodilator. Fasudil was
`administrated 30mg with 1 mg/min. Hemodynamic data were measured using Swan-Ganz
`catheter until 60 minutes after starting administration of fasudil. Hemodynamic and arterial
`blood gas data of baseline and the lowest total pulmonary resistance (TPR) time were
`compared. Results: The lowest TPR time was within 30 to 60 minutes after administration.
`Administration of fasudil significantly decreased TPR from 13.6 :t 6.8 U to 10.3 :t 4.9 U (-23.2
`:t 9.2 %, p < 0.001) and mean pulmonary arterial pressure (mPAP) from 43.6 :t 14.5 mmHg
`to 38.8 :t 13.9 mmHg (-11.6 :t 10.4 %, p < 0.02). Cardiac index (Cl) was significantly
`increased from 2.39 :t 0.66 Umin/m2 to 2.74 :t 0.73 Umin/m2 (+ 16.5 :t 15.1 %, p < 0.01).
`Although TPR was equally decreased in both primary and secondary PH, the changes in the
`parameters that prescribed TPR, namely Cl and mPAP, were different between the two groups
`subjects. Increased Cl was a major factor into reducing TPR in primary PH, while reduced mPAP
`
`Liquidia's Exhibit 1096
`Page 7
`
`