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21 results on '"Zapol, Warren M."'

1. Contributors

Author

Ahluwalia, Amrita, primary, Akaike, Takaaki, additional, Álvarez, María Noel, additional, Alvarez, Roger A., additional, Basudhar, Debashree, additional, Bianco, Christopher L., additional, Billiar, Timothy R., additional, Bovee, Rhea C., additional, Brookes, Paul S., additional, Castro, Laura, additional, Cheng, Robert Y.S., additional, Correa-Aragunde, Natalia, additional, Cortese-Krott, Miriam M., additional, Deng, Meihong, additional, Du, Qiang, additional, Dulce, Raul A., additional, Förstermann, Ulrich, additional, Feelisch, Martin, additional, Fleming, Ingrid, additional, Foresi, Noelia, additional, Freeman, Bruce A., additional, Fritsch, Julia, additional, Fukuto, Jon M., additional, Geller, David A., additional, Gladwin, Mark T., additional, Grasemann, Hartmut, additional, Greer, Madison, additional, Hare, Joshua M., additional, Hickok, Jason R., additional, Hogg, Neil, additional, Holguin, Fernando, additional, Ichinose, Fumito, additional, Jones, Daniel A., additional, Kalyanaraman, Balaraman, additional, Kato, Gregory J., additional, Kelley, Eric E., additional, Kelm, Malte, additional, Kevil, Christopher G., additional, Kevil, Christopher, additional, Kim-Shapiro, Daniel B., additional, Koesling, Doris, additional, Kramer, Christian M., additional, Kulandavelu, Shathiyah, additional, Kumagai, Yoshito, additional, Lamattina, Lorenzo, additional, Lancaster, Jack R., additional, Lei, Zhao, additional, Li, Huige, additional, Lipton, Stuart A., additional, Loughran, Patricia A., additional, Lundberg, Jon O., additional, Mergia, Evanthia, additional, Morris, Claudia R., additional, Nagy, Péter, additional, Nakamura, Tomohiro, additional, Papapetropoulos, Andreas, additional, Patel, Rakesh P., additional, Pekarova, Michaela, additional, Piacenza, Lucía, additional, Prolo, Carolina, additional, Ríos, Natalia, additional, Radi, Rafael, additional, Rathod, Krishnaraj S., additional, Ridnour, Lisa A., additional, Rubbo, Homero, additional, Russwurm, Michael, additional, Sawa, Tomohiro, additional, Schulman, Ivonne Hernandez, additional, Scott, Jeremy A., additional, Shiva, Sruti, additional, Somasundaram, Veena, additional, Straub, Adam C., additional, Szabo, Csaba, additional, Thomas, Douglas D., additional, Toscano, John P., additional, Trostchansky, Andres, additional, Vasudevan, Divya, additional, Weitzberg, Eddie, additional, Wink, David A., additional, Winnica, Daniel E., additional, Wood, Katherine C., additional, Xu, Li, additional, Yuan, Shuai, additional, Zapol, Warren M., additional, and Zielonka, Jacek, additional

Published
2017
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3. Contributors

Author

Adhikary, Sanjib, primary, Aguilar, Jorge, additional, Ahere, Charles, additional, Ahmed, Moustafa, additional, Ahn, Jane C., additional, Akhtar, Shamsuddin, additional, Albert, David B., additional, Aldawoodi, Nasrin N., additional, Algren, John T., additional, Almeida-Chen, Gracie, additional, Amar, David, additional, Anastasian, Zirka H., additional, Aniskevich, Stephen, additional, Aronson, Solomon, additional, Arora, Harendra, additional, Asopa, Amit, additional, Atkins, Joshua H., additional, Augoustides, John G., additional, Azam, Mohammad Fareed, additional, Bachman, Catherine R., additional, Bacon, Douglas R., additional, Badley, Andrew D., additional, Baird, Emily, additional, Baldwin, Alethia, additional, Ball, Ryan, additional, Baluch, Amir, additional, Bandola, David, additional, Banks, Shawn, additional, Barash, Paul G., additional, Barrett, Kathleen E., additional, Beaman, Shawn T., additional, Beathe, Jonathan C., additional, Beatie, Christopher D., additional, Beattie, W. Scott, additional, Bechtle, Perry S., additional, Benzinger, G. Richard, additional, Berkow, Lauren, additional, Berman, Jeffrey M., additional, Bernstein, Wendy K., additional, Berry, Arnold J., additional, Berry, Frederic, additional, Berth, Ulrike, additional, Bethune, Walter, additional, Bhambhani, Sumita, additional, Bharadwaj, Shobana, additional, Bhatt, Neil, additional, Billings, Frederic T., additional, Binstock, Wendy B., additional, Birnbach, David J., additional, Bishop, Michael, additional, Black, Stephanie, additional, Blanchette, Mary A., additional, Blum, James M., additional, Boddu, Krishna, additional, Bonasera, Lara, additional, Boortz-Marx, Richard L., additional, Borel, Cecil O., additional, Botz, Gregory H., additional, Boucek, Charles D., additional, Bradford, William, additional, Brainard, Jason C., additional, Braunfeld, Michelle, additional, Braveman, Ferne R., additional, Bravo-Fernandez, Caridad, additional, Breen, Peter H., additional, Brennan, Marjorie, additional, Brentjens, Tricia, additional, Brockel, Megan A., additional, Brodsky, Jay B., additional, Bromberg, Todd A., additional, Broussard, Adam J., additional, Broussard, Chris, additional, Labrie-Brown, Carmen, additional, Brown, Robert H., additional, Brudney, Charles S., additional, Brull, Sorin J., additional, Brunson, Claude, additional, Bryson, Trent, additional, Buchowski, Jacob M., additional, Budac, Stefan, additional, Bush, Zachary D., additional, Butterworth, John, additional, Calo, Lisbeysi, additional, Canlas, Christopher, additional, Cannon, Ayana, additional, Cantie, Shawn M., additional, Caplan, Lisa, additional, Caruso, Marco, additional, Cattano, Davide, additional, Cauldwell, Charles B., additional, Cavallone, Laura, additional, Cereda, Maurizio, additional, Chalifoux, Thomas M., additional, Chan, Susan, additional, Cheek, Theodore G., additional, Chen, Alexander, additional, Cherry, Samuel A., additional, Cheung, Albert T., additional, Chien, Grace L., additional, Choi, Peter T., additional, Ciarallo, Christopher, additional, Cladis, Franklyn, additional, Clapcich, Anthony J., additional, Clark, Richard B., additional, Cohen, Mindy, additional, Cohen, Neal H., additional, Cohen, Robert I., additional, Cohn, Stephan J., additional, Conran, Aisling, additional, Cook, Richard I., additional, Coombs, Randall F., additional, Corda, David M., additional, Cormican, Daniel, additional, Cousin, Darren, additional, Cowell, Vincent S., additional, Cox, Lyndsey, additional, Craigo, Paula A., additional, Cross, Richard C., additional, Cucchiara, Roy F., additional, Daily, William H., additional, Dalal, Gaurang, additional, Dalal, Priti, additional, Danekas, Michael, additional, Darwish, Ahmed M., additional, Darwish, Ribal, additional, Daves, Suanne M., additional, Davis, Kathleen, additional, Davis, Peter J., additional, De Witt, Bracken J., additional, Delphin, Ellise, additional, Deshpande, Seema, additional, Desiderio, Dawn P., additional, Desvarieux, Tricia, additional, Diaz, Laura K., additional, Diez, Christian, additional, Dixit, Sanjay, additional, Dogra, Meenakshi, additional, Domino, Karen B., additional, Dorhauer, Kathryn, additional, Dorman, Todd, additional, Doussan, Don D., additional, Duke, James, additional, Duncan, Ann C., additional, Dupont, Frank W., additional, Dziewit, Andrew, additional, Easdown, L. Jane, additional, Easley, R. Blaine, additional, Ebert, Thomas J., additional, Eckmann, David M., additional, Egan, Talmage D., additional, Eisdorfer, Seth, additional, Elkassabany, Nabil M., additional, Ellender, Ryan P., additional, Emory, Logan S., additional, Espinosa, Monique, additional, Everett, Lucinda L., additional, Faraday, Nauder, additional, Fehr, James J., additional, Feld, James M., additional, Fenton, Lynn A., additional, Ferguson, Laura H., additional, Fiegel, Matthew, additional, Fields, Aaron M., additional, Finlayson, Gordon N., additional, Finley, Alan, additional, Fischer, Gregory W., additional, Fiskum, Gary, additional, Fitzpatrick, Molly, additional, Flatto, Russell, additional, Fleisher, Lee A., additional, Flower, Ronda, additional, Folgueras, Annette G., additional, Forte, Patrick J., additional, Foss, Joseph F., additional, Fox, Charles J., additional, Furman, William R., additional, Gaiser, Robert, additional, Gambling, David R., additional, Gardiner, Scott, additional, Garvey, Matthew L., additional, Gaupp, Abraham C., additional, Gayer, Steven, additional, Geiduschek, Jeremy M., additional, Gencorelli, Frank, additional, Gewirtz, Eric, additional, Ghani, Ghaleb A., additional, Gibbs, Charles P., additional, Gibson, Jeremy L., additional, Gilbert, Lori, additional, Gingrich, Kevin J., additional, Ginsburg, Gregory, additional, Giordano, Christopher, additional, Goepfert, Christine E., additional, Gomez, Hernando, additional, Gomez, Santiago, additional, Goodman, Alanna E., additional, Goodman, Stephanie R., additional, Gottlieb, Alexandru, additional, Gottlieb, Ori, additional, Gottschalk, Allan, additional, Goudra, Basavana Gouda, additional, Gould, Harry J., additional, Gravenstein, Nikolaus, additional, Graybill, Megan, additional, Greeley, William J., additional, Guffey, Patrick, additional, Haddadin, Ala Sami, additional, Hagen, John G., additional, Hakim, Karim Abdel, additional, Hall, Michael, additional, Halliday, N. James, additional, Hannallah, Raafat S., additional, Hansen, Jeremy, additional, Hanson, C. William, additional, Hantler, Charles B., additional, Harris, Andrew P., additional, Hastie, Jonathan, additional, Hawney, Henry A., additional, Heard, Stephen O., additional, Heavner, James E., additional, Hecker, James G., additional, Hein, Elizabeth A., additional, Heitmiller, Eugenie, additional, Helfaer, Mark, additional, Heller, Lori B., additional, Hemphill, Andrew, additional, Hendrickse, Adrian, additional, Hensley, Frederick A., additional, Herrick, Ian A., additional, Hester, Douglas, additional, Heyer, Eric J., additional, Higgins, Michael S., additional, Hines, Roberta, additional, Hogue, Charles W., additional, Holroyd, Kenneth J., additional, Holt, Natalie F., additional, Howell, Simon J., additional, Huda, Faisal, additional, Hude, Keith E., additional, Hughes, Hayden R., additional, Hunter, James M., additional, Hymel, Brad J., additional, Ibinson, James W., additional, Iles, Karen E., additional, Insoft, Robert M., additional, Isono, Shiroh, additional, Ivashkov, Yulia, additional, Jachna, Bozena R., additional, Jankowska, Anna, additional, Janosy, Norah, additional, Jayaraman, Arun L., additional, Jimenez, Nathalia, additional, Johnson, Judy G., additional, Jones, Lyndia, additional, Jooste, Edmund H., additional, Kain, Zeev N., additional, Kalangie, Maudy, additional, Kalarickal, Philip L., additional, Kamel, Ihab, additional, Kang, Mia, additional, Kangrga, Ivan, additional, Kapoor, Ravish, additional, Karl, Helen W., additional, Karsanac, Christopher, additional, Karthik, Swaminathan, additional, Katz, Jeffrey A., additional, Kaye, Alan, additional, Kaye, Adam M., additional, Kaynar, A. Murat, additional, Kenepp, Nancy B., additional, Kertai, Miklos D., additional, Keyes, Mary A., additional, Khan, Sarah, additional, Khoche, Swapnil, additional, Kim, David Y., additional, Kim, Jerry H., additional, King, Kimberly M., additional, Kirsch, Jeffrey, additional, Klopman, Matthew A., additional, Knight, Paul R., additional, Koblin, Donald D., additional, Kofke, W. Andrew, additional, Kopp, Vincent J., additional, Koveleskie, Joseph R., additional, Kowalczyk, Courtney, additional, Kozmenko, Valeriy V., additional, Krummen, Kaylyn, additional, Kudchadkar, Sapna R., additional, Kudrick, Nathan, additional, Kung, Adrienne, additional, Kurth, C. Dean, additional, Kyle, Robert, additional, LaFleur, J. Lance, additional, Lai, Jason G., additional, Lalwani, Kirk, additional, Lanier, William L., additional, Larson, Dawn M., additional, Layman, Richard M., additional, Lee, Chris C., additional, Lema, Mark J., additional, Lenox, W. Casey, additional, Leung, Jacqueline M., additional, Levitt, Roy C., additional, Levy, Jerrold H., additional, Lichtor, J. Lance, additional, Lin, Charles, additional, Lin, Sharon L., additional, Lindeman, Karen S., additional, Lirette, Lesley, additional, Litman, Ronald S., additional, Liu, Qianjin, additional, Liu, Renyu, additional, Liu, Wen-Shin, additional, Lockman, Justin, additional, Loftness, Stanley L., additional, London, Martin J., additional, Lumb, Philip D., additional, Lupa, M. Concetta, additional, Lynn, Anne Marie, additional, Mahendran, Devi, additional, Mako, Jeffrey, additional, Malhotra, Anuj, additional, Malhotra, Vinod, additional, Malinow, Andrew M., additional, Mandabach, Mark G., additional, Mangano, Dennis T., additional, Mansoor, Sobia, additional, Maranets, Inna, additional, Mark, Jonathan B., additional, Markovic, Sinisa, additional, Marsh, H. Michael, additional, Martin, Choendal, additional, Martin, Nicole D., additional, Martz, Douglas, additional, Matei, Veronica A., additional, Mathews, Letha, additional, Maxwell, Lynne G., additional, McArdle, Philip, additional, McCarren, John P., additional, McClain, Brenda C., additional, McClure, Brian, additional, McDade, William A., additional, McGoldrick, Kathryn E., additional, McGrath, Brian J., additional, McHugh, Gregory L., additional, McIlroy, David, additional, McKeown, Jason, additional, McLoughlin, Thomas M., additional, McRae, R. Yan, additional, Meadow, William L., additional, Menda, Sameer, additional, Merritt, William T., additional, Metro, David G., additional, Mets, Berend, additional, Mikhaeil, Hosni, additional, Miller, David W., additional, Miller, Jessica, additional, Minhaj, Mohammed, additional, Mirski, Marek A., additional, Mitter, Nanhi, additional, Mittnacht, Alexander J.C., additional, Modak, Raj K., additional, Moine, Pierre, additional, Monitto, Constance L., additional, Month, Richard C., additional, Moon, Richard E., additional, Moore, Laurel E., additional, Moore, Roger A., additional, Moore, Thomas A., additional, Morrison, Debra E., additional, Moss, Jonathan, additional, Moyers, John R., additional, Muir, Jesse J., additional, Munson-Young, Adam J., additional, Muravchick, Stanley, additional, Murkin, John M., additional, Nagele, Peter, additional, Nagi, Peter A., additional, Nahrwold, Daniel A., additional, Nahrwold, Michael L., additional, Naik, Madhavi, additional, Navaratnam, Manchula, additional, Nebbia, Stephan P., additional, Nelson, Priscilla, additional, Nguyen, Thai T., additional, Nguyen, Viet, additional, Nikolaidis, Stavroula, additional, Nisnevitch, Zoulfira, additional, Njoku, Dolores B., additional, Njoku, Mary J., additional, Norris, Edward J., additional, Nwokolo, Omonele O., additional, Nyhan, Daniel, additional, O'Byrne, William T., additional, Ochroch, Edward A., additional, Oken, Andrew, additional, Orgain, Nathan, additional, Oriol, Nancy E., additional, Orozco, Pedro, additional, Ostermeier, Andreas M., additional, Ovassapian, Andranik, additional, Ozcan, Mehmet S., additional, Padnos, Ira, additional, Pai, Sheela S., additional, Pal, Nirvik, additional, Palaniappan, Dhamodaran, additional, Palmer, Susan K., additional, Palte, Howard D., additional, Pan, Wei, additional, Panzer, Oliver, additional, Pappachan, Sibi, additional, Passannante, Anthony, additional, Patel, Dennis A., additional, Patel, Dilipkumar K., additional, Patel, Kirit M., additional, Patel, Samir, additional, Patel, Shalin, additional, Pathak, Sanup, additional, Patt, Minda L., additional, Pauldine, Ronald W., additional, Pawelek, Olga, additional, Pawelek, Tim, additional, Paydar, Kiarash, additional, Pearl, Ronald G., additional, Peeters-Asdourian, Christine, additional, Perela, Padmavathi R., additional, Petrovitch, Charise T., additional, Petrozza, Patricia H., additional, Phillips, Dennis, additional, Phillips, Mark C., additional, Piefer, Christine, additional, Pierre, Edgar J., additional, Pinson, S. William, additional, Pivalizza, Evan G., additional, Planinsic, Raymond M., additional, Poldermans, Don, additional, Pomerantz, Joel M., additional, Pope, Jason E., additional, Popescu, Wanda M., additional, Porche, Vivian H., additional, Porhomayon, Jahan, additional, Portnoy, Dmitry, additional, Postle, Corinne K., additional, Primeaux, Paul J., additional, Prough, Donald S., additional, Puskas, Ferenc, additional, Puyo, Carlos A., additional, Quiggle, Forrest, additional, Rabb, Mary, additional, Rae, Bronwyn R., additional, Rafique, Muhammad B., additional, Raiten, Jesse M., additional, Rajagopal, Arvind, additional, Rajagopal, Srinivasan, additional, Rajpal, Gaurav, additional, Ramamoorthy, Chandra, additional, Rampil, Ira J., additional, Ramsay, James G., additional, Ramsey, James A., additional, Rao, Vidya N., additional, Ratsiu, Joana, additional, Read, Selina, additional, Reddy, Ronjeet, additional, Reduque, Leila L., additional, Reich, David L., additional, Ricketts, Karene, additional, Ricks, Cameron, additional, Riedel, Bernhard, additional, Rimal, Jyotsna, additional, Rinehart, Joseph, additional, Riopelle, James M., additional, Rizza, Stacey A., additional, Robertson, Amy C., additional, Robinson, Stephen, additional, Rock, Peter, additional, Rodriguez-Blanco, Yillam F., additional, Roizen, Michael F., additional, Roke, Daniel M., additional, Romeo, Ryan, additional, Rosa, Joseph, additional, Rosen, David A., additional, Rosen, Kathleen, additional, Rosenbaum, Stanley H., additional, Rosenberg, Andrew D., additional, Rosenberg, Andrew L., additional, Rosenberg, Henry, additional, Rosenblatt, Meg A., additional, Roth, Steven, additional, Rothman, Brian, additional, Rountree, Justin L., additional, Rowan, Matthew J., additional, Rozner, Marc, additional, Rubin, Ryan, additional, Rupp, Stephen M., additional, Russell, W. John, additional, Russo, Thomas A., additional, Sabartinelli, Alecia L., additional, Sakai, Tetsuro, additional, Salinas, Orlando J., additional, Samm, Paul L., additional, Samuel, Jibin, additional, Sandven, Tor, additional, Sanford, Ted J., additional, Sappenfield, Joshua W., additional, Saravanan, Ponnusamy, additional, Sathishkumar, Subramanian, additional, Schlichter, R. Alexander, additional, Schnell, Eric, additional, Schreibman, David L., additional, Schubert, Armin, additional, Schulman, Peter, additional, Schultz, Todd A., additional, Schwartz, Alan Jay, additional, Schwartz, Jamie McElrath, additional, Schwartz, Jeffrey J., additional, Scott, Benjamin K., additional, Seltzer, Joseph L., additional, Seres, Tamas, additional, Sessler, Daniel I., additional, Sethna, Navil F., additional, Setty, Amar, additional, Shabaz, Paul W., additional, Shah, Pranav, additional, Shah, Saroj Mukesh, additional, Sharifpour, Milad, additional, Shay, Joanne, additional, Shepherd, Jay, additional, Shiffrin, Jeffrey S., additional, Shindell, Marina, additional, Siker, Daniel, additional, Silverman, Richard, additional, Simon, Brett A., additional, Singh, Nina, additional, Sinha, Ashish C., additional, Sladen, Robert N., additional, Slevin, Kieran A., additional, Sloan, Tod B., additional, Smith, Kathleen, additional, Smith, Timothy E., additional, Smoot, Victoria, additional, Snegovskikh, Denis, additional, Soifer, Betsy Ellen, additional, Solorzano, Molly, additional, Sonner, James M., additional, Sophocles, Aris, additional, Sparrow, James A., additional, Spiegel, Joan, additional, Spiess, Bruce D., additional, Sripada, Ramprasad, additional, Stead, Stanley W., additional, Stearns, Joshua D., additional, Stees, Kelly, additional, Steffey, Clinton, additional, Stemland, Christopher, additional, Stene, John, additional, Stephens, Christopher T., additional, Stierer, Tracey L., additional, Stokes, O. Jameson, additional, Stolp, Bryant W., additional, Stowe, David F., additional, Strickland, Ted, additional, Strom, Suzanne, additional, Sullivan, Erin A., additional, Sumler, Michele, additional, Sun, Dajin, additional, Sun, Lena, additional, Sung, Esther, additional, Swanson, Veronica C., additional, Szolnoki, Judit, additional, Talarico, Joe, additional, Tan, Gee Mei, additional, Tang, Darryl T., additional, Tarasi, Paul, additional, Tempelhoff, René, additional, Tetzlaff, John E., additional, Thorne, Alisa C., additional, Thung, Arlyne, additional, Tilak, Vasanti, additional, Tobin, Kate, additional, Tobin, Joseph R., additional, Tobin, Michael J., additional, Todd, R. David, additional, Tomlinson, Matthew, additional, Toung, Thomas J., additional, Tran, Lien B., additional, Tran, Minh Chau Joe, additional, Tremper, Kevin K., additional, Tsai, Sanyo, additional, Tseng, George S., additional, Tuman, Kenneth J., additional, Tung, Avery, additional, Tung, Cynthia, additional, Twersky, Rebecca, additional, Twite, Mark, additional, Ulatowski, John A., additional, Urban, Michael, additional, Vallejo, Manuel C., additional, Vannucci, Andrea, additional, Varon, Albert J., additional, Vasudevan, Anasuya, additional, Viswanathan, Susheela, additional, Vitin, Alexander A., additional, Voelckel, Wolfgang, additional, Walia, Ann, additional, Wall, Russell T., additional, Wallace, Terrence, additional, Wang, Shu-Ming, additional, Warltier, David C., additional, Waskell, Lucy, additional, Watkins, Scott, additional, Wedel, Denise, additional, Weiss, Stuart J., additional, Weissman, Charles, additional, Weitzel, Nathaen, additional, Weller, Gregory, additional, Whitney, Gina, additional, Whittington, Robert A., additional, Wilkerson, Danny, additional, Wilkes, Nancy C., additional, Williams, Michael, additional, Windsor, Jimmy, additional, Wittels, Bernard, additional, Wolff, Gregory A., additional, Wong, Andrew K., additional, Woods, Stacie N., additional, Wright, A.J., additional, Xie, Zheng, additional, Young, Christopher C., additional, Yuan, Ian, additional, Yudkowitz, Francine S., additional, Zaidan, James R., additional, Zanaboni, Paul, additional, Zapol, Warren M., additional, Zimmerman, Angela, additional, and Zwass, Maurice S., additional

Published
2011
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6. Contributors

Author

Abel, Ted G., primary, Afonin, Olga N., additional, Allen, Paul D., additional, Andrews, J. Jeffrey, additional, Ang-Lee, Michael, additional, Apfel, Christian C., additional, Arnold, William P., additional, Aronson, Solomon, additional, Bader, Angela M., additional, Baker, David, additional, Baraka, Anis, additional, Barbeito, Atilio, additional, Barker, Steven J., additional, Bar-Yosef, Shahar, additional, Berde, Charles B., additional, Berkowitz, Darryl H., additional, Birnbach, David J., additional, Bogod, David, additional, Brockwell, Russell C., additional, Brown, David L., additional, Browne, Ingrid M., additional, Cahalan, Michael K., additional, Camporesi, Enrico M., additional, Campos, Javier H., additional, Cassorla, Lydia, additional, Coté, Charles J., additional, Dalens, Bernard J., additional, Deutschman, Clifford S., additional, Dieckmann, Peter, additional, Diwan, Sudhir, additional, Drummond, John C., additional, Dutton, Richard P., additional, Eckmann, David M., additional, Eger, Edmond I., additional, Eich, Christoph, additional, Eng, Matthew R., additional, Eriksson, Lars I., additional, Eskaros, Stephen M., additional, Farber, Neil E., additional, Feldman, Marc Allan, additional, Fischer, Stephen P., additional, Fleisher, Lee A., additional, Flood, Pamela, additional, Fukuda, Kazuhiko, additional, Gaba, David M., additional, Ganter, Michael T., additional, Gelb, Adrian W., additional, Gelman, Simon, additional, Glass, Peter S.A., additional, Glick, David B., additional, Goodnough, Lawrence T., additional, Goswami, Sumeet, additional, Grasso, Salvatore, additional, Gray, Andrew T., additional, Greeley, William J., additional, Gregory, George A., additional, Grigore, Alina M., additional, Grissom, Thomas E., additional, Gropper, Michael A., additional, Haddad, Fouad Salim, additional, Hanson, C. William, additional, Hauser, Michael C., additional, Hedenstierna, Göran, additional, Heitmiller, Eugenie S., additional, Hemmings, Hugh C., additional, Henderson, John, additional, Hillel, Zak, additional, Hofer, Christoph K., additional, Horlocker, Terese T., additional, Howard, Steven K., additional, Huang, Yuguang, additional, Hüpfl, Michael, additional, Hurley, Robert W., additional, Ichinose, Fumito, additional, Irefin, Samuel A., additional, Johnson, Ken B., additional, Joris, Jean L., additional, Kaye, Alan D., additional, Kelz, Max B., additional, Kindscher, James D., additional, Kohl, Benjamin A., additional, Kopf, Andreas, additional, Lachmann, Burkhard, additional, Lam, Arthur M., additional, Landesberg, Giora, additional, Larson, Merlin D., additional, Lee, Jae-Woo, additional, Lema, Guillermo, additional, Leslie, Kate, additional, Lien, Cynthia A., additional, Litt, Lawrence, additional, Liu, Linda, additional, Lubarsky, David A., additional, Mahla, Michael E., additional, Malhotra, Vinod, additional, Mark, Jonathan B., additional, Martin, Jackie L., additional, Martinez, Elizabeth A., additional, Martinez-Ruiz, Ricardo, additional, Jeevendra Martyn, J.A., additional, Mascia, Luciana, additional, Mashour, George A., additional, Maze, Mervyn, additional, McCunn, Maureen, additional, McEvoy, Matthew D., additional, McGlinch, Brian P., additional, Mets, Berend, additional, Miller, Ronald D., additional, Monk, Terri G., additional, Moon, Richard E., additional, Mori, Kenjiro, additional, Moss, Jonathan, additional, Mushlin, Phillip S., additional, Nagele, Peter, additional, Naguib, Mohamed, additional, Nakao, Shinichi, additional, Namiki, Akiyoshi, additional, Nathan, Aruna T., additional, Neligan, Patrick J., additional, Newman, Stanton P., additional, Nicholau, Dorre, additional, Niemann, Claus U., additional, Nishanian, Ervant, additional, Norris, Edward J., additional, Nuevo, Florian R., additional, Nussmeier, Nancy A., additional, O'Connor, Christopher J., additional, O'Hara, Jerome, additional, Pagel, Paul S., additional, Papadakos, Peter J., additional, Patel, Anil, additional, Patel, Piyush M., additional, Pauldine, Ronald, additional, Pearce, Robert A., additional, Perouansky, Misha, additional, Pessah, Isaac N., additional, Pittet, Jean-François, additional, Pratt, Phillip F., additional, Pronovost, Peter J., additional, Rall, Marcus, additional, Rampil, Ira J., additional, Ranieri, V. Marco, additional, Rasmussen, Lars, additional, Reves, J.G., additional, Ricci, Zaccaria, additional, Riopelle, James M., additional, Rockford, Melissa, additional, Roizen, Michael F., additional, Ronco, Claudio, additional, Rosenbaum, Stanley H., additional, Roth, Steven, additional, Rothenberg, David M., additional, Rozner, Marc A., additional, Sarwar, Muhammad F., additional, Schroeder, Rebecca A., additional, Schwartz, Allan Jay, additional, Schwartz, Andrew, additional, Schwarzenberger, Johanna C., additional, Schwinn, Debra A., additional, Searles, Bruce E., additional, Sessler, Daniel I., additional, Seubert, Christoph N., additional, Shafer, Steven L., additional, Shaw, Andrew, additional, Shingu, Koh, additional, Sieber, Frederick E., additional, Simpson, Sir Peter, additional, Sinha, Ashish C., additional, Sladen, Robert N., additional, Slaughter, Thomas F., additional, Slinger, Peter D., additional, Souter, Michael J., additional, Stafford-Smith, Mark, additional, Stanski, Donald R., additional, Stein, Christoph, additional, Stensrud, Paul E., additional, Strichartz, Gary R., additional, Stygall, Jan, additional, Sudheendra, Vijayendra, additional, Sun, Lena S., additional, Sweitzer, BobbieJean, additional, Szocik, James, additional, Tempe, Deepak K., additional, Tremper, Kevin K., additional, Tuman, Kenneth J., additional, Urban, Michael K., additional, Van Norman, Gail A., additional, Vezina, Daniel P., additional, Viby-Mogensen, Jørgen, additional, Waisel, David B., additional, Warltier, David C., additional, Wedel, Denise J., additional, Weissman, Charles, additional, White, Paul F., additional, White, Roger D., additional, Wiener-Kronish, Jeanine P., additional, Wu, Christopher L., additional, Yamakage, Michiaki, additional, Yost, C. Spencer, additional, Young, William L., additional, Yuan, Chun-Su, additional, Zapol, Warren M., additional, Zhou, Jie, additional, and Zwass, Maurice S., additional

Published
2010
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10. Development of nitric oxide generators to produce high-dose nitric oxide for inhalation therapy.

Author

Yu B, Wanderley HV, Gianni S, Carroll RW, Ichinose F, Zapol WM, and Berra L

Subjects
Respiratory Therapy, Lung, Administration, Inhalation, Oxygen, Nitric Oxide, Nitrogen Dioxide
Abstract

Background: Several nitric oxide (NO) generating devices have been developed to deliver NO between 1 part per million (ppm) and 80 ppm. Although inhalation of high-dose NO may exert antimicrobial effects, the feasibility and safety of producing high-dose (more than 100 ppm) NO remains to be established. In the current study, we designed, developed, and tested three high-dose NO generating devices., Methods: We constructed three NO generating devices: a double spark plug NO generator, a high-pressure single spark plug NO generator, and a gliding arc NO generator. The NO and NO 2 concentrations were measured at different gas flows and under various atmospheric pressures. The double spark plug NO generator was designed to deliver gas through an oxygenator and mixing with pure oxygen. The high-pressure and gliding arc NO generators were used to deliver gas through a ventilator into artificial lungs to mimic delivering high-dose NO in the clinical settings. The energy consumption was measured and compared among the three NO generators., Results: The double spark plug NO generator produced 200 ± 2 ppm (mean ± SD) of NO at gas flow of 8 L/min (or 320 ± 3 ppm at gas flow of 5 L/min) with electrode gap of 3 mm. The nitrogen dioxide (NO 2 ) levels were below 3.0 ± 0.1 ppm when mixing with various volumes of pure oxygen. The addition of a second generator increased the delivered NO from 80 (with one spark plug) to 200 ppm. With the high-pressure chamber, the NO concentration reached 407 ± 3 ppm with continuous air flow at 5 L/min when employing the 3 mm electrode gap under 2.0 atmospheric pressure (ATA). When compared to 1 ATA, NO production was increased 22% at 1.5 ATA and 34% at 2 ATA. The NO level was 180 ± 1 ppm when connecting the device to a ventilator with a constant inspiratory airflow of 15 L/min, and NO 2 levels were below 1 (0.93 ± 0.02) ppm. The gliding arc NO generator produced up to 180 ± 4 ppm of NO when connecting the device to a ventilator, and the NO 2 level was below 1 (0.91 ± 0.02) ppm in all testing conditions. The gliding arc device required more power (in watts) to generate the same concentrations of NO when compared to double spark plug or high-pressure NO generators., Conclusions: Our results demonstrated that it is feasible to enhance NO production (more than 100 ppm) while maintaining NO 2 level relatively low (less than 3 ppm) with the three recently developed NO generating devices. Future studies might include these novel designs to deliver high doses of inhaled NO as an antimicrobial used to treat upper and lower respiratory tract infections., Competing Interests: Declaration of competing interest All authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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11. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia.

Author

Safaee Fakhr B, Di Fenza R, Gianni S, Wiegand SB, Miyazaki Y, Araujo Morais CC, Gibson LE, Chang MG, Mueller AL, Rodriguez-Lopez JM, Ackman JB, Arora P, Scott LK, Bloch DB, Zapol WM, Carroll RW, Ichinose F, and Berra L

Subjects
Administration, Inhalation, COVID-19 complications, COVID-19 virology, Dose-Response Relationship, Drug, Humans, Nitric Oxide pharmacology, Nitric Oxide therapeutic use, Pneumonia, Viral complications, Hospitalization, Nitric Oxide administration & dosage, Pneumonia, Viral drug therapy, Respiration drug effects, COVID-19 Drug Treatment
Abstract

Background: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19)., Methods: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients., Results: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up., Conclusions: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae., (Published by Elsevier Inc.)

Published
2021
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12. Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects.

Author

Gianni S, Morais CCA, Larson G, Pinciroli R, Carroll R, Yu B, Zapol WM, and Berra L

Subjects
Administration, Inhalation, Adult, Female, Humans, Male, Respiration, Drug Delivery Systems instrumentation, Drug Delivery Systems methods, Nitric Oxide administration & dosage
Abstract

Background: There is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described., Methods: We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO 2 ) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO 2 of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system., Results: The system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0-50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow. The calcium hydroxide scavenger reduced the inhaled NO 2 concentration on average 0.9 ppm (95% CI -1.58, -0.22; p = .01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8±10.74 ppm, with inspired NO 2 levels of 0.7±0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05±0.58 to 2.26±0.47%., Conclusions: The system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
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13. Intratracheal injection of nitric oxide, generated from air by pulsed electrical discharge, for the treatment of pulmonary hypertension in awake ambulatory lambs.

Author

Yu B, Zadek F, Fischbach A, Wiegand SB, Berra L, Bloch DB, and Zapol WM

Subjects
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid administration & dosage, Administration, Inhalation, Air, Animals, Electricity, Hypertension, Pulmonary chemically induced, Infusions, Intravenous, Nitric Oxide administration & dosage, Nitric Oxide analysis, Sheep, Trachea chemistry, Vasodilation drug effects, Hypertension, Pulmonary drug therapy, Nitric Oxide pharmacology, Wakefulness drug effects
Abstract

Objectives: To test the feasibility, safety, and efficacy of intratracheal delivery of nitric oxide (NO) generated from air by pulsed electrical discharge via a Scoop catheter., Study Design: We studied healthy 3- to 4-month-old lambs weighing 34 ± 4 kg (mean ± SD, n = 6). A transtracheal Scoop catheter was inserted through a cuffed tracheostomy tube. U46619 was infused to increase mean pulmonary arterial pressure (mPAP) from 16 ± 1 to 32 ± 3 mmHg (mean ± SD). Electrically generated NO was delivered via the Scoop catheter to awake lambs. A sampling line, to monitor NO and nitrogen dioxide (NO 2 ) levels, was placed in the distal trachea of the lambs. The effect of varying doses of electrically generated NO, produced continuously, on pulmonary hypertension was assessed., Results: In awake lambs with acute pulmonary hypertension, NO was continuously delivered via the Scoop catheter at 400 ml/min. NO induced pulmonary vasodilation. NO 2 levels, measured in the trachea, were below 0.5 ppm at intratracheal NO doses of 10-80 ppm. No changes were detected in the levels of methemoglobin in blood samples before and after 5 min of NO breathing., Conclusions: Continuously delivering electrically generated NO through a Scoop catheter produces vasodilation of the pulmonary vasculature of awake lambs with pulmonary hypertension. Transtracheal NO delivery may provide a long-term treatment for patients with chronic pulmonary hypertension as an outpatient without requiring a mask or tracheal intubation., Competing Interests: Declaration of competing interest Other authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
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14. Pharmacological preconditioning with inhaled nitric oxide (NO): Organ-specific differences in the lifetime of blood and tissue NO metabolites.

Author

Nagasaka Y, Fernandez BO, Steinbicker AU, Spagnolli E, Malhotra R, Bloch DB, Bloch KD, Zapol WM, and Feelisch M

Subjects
Administration, Inhalation, Animals, Brain metabolism, Feasibility Studies, Freezing, Half-Life, Kidney metabolism, Lung metabolism, Male, Mice, Inbred C57BL, Myocardial Reperfusion Injury metabolism, Myocardium metabolism, Nitric Oxide blood, Nitrites blood, Nitrites metabolism, Nitrites urine, Organ Specificity, S-Nitrosothiols metabolism, Tissue Distribution, Myocardial Reperfusion Injury prevention & control, Nitric Oxide administration & dosage, Nitric Oxide metabolism
Abstract

Background: Endogenous nitric oxide (NO) may contribute to ischemic and anesthetic preconditioning while exogenous NO protects against ischemia-reperfusion (I/R) injury in the heart and other organs. Why those beneficial effects observed in animal models do not always translate into clinical effectiveness remains unclear. To mitigate reperfusion damage a source of NO is required. NO inhalation is known to increase tissue NO metabolites, but little information exists about the lifetime of these species. We therefore sought to investigate the fate of major NO metabolite classes following NO inhalation in mice in vivo., Methods: C57BL/6J mice were exposed to 80 ppm NO for 1 h. NO metabolites were measured in blood (plasma and erythrocytes) and tissues (heart, liver, lung, kidney and brain) immediately after NO exposure and up to 48 h thereafter. Concentrations of S-nitrosothiols, N-nitrosamines and NO-heme products as well as nitrite and nitrate were quantified by gas-phase chemiluminescence and ion chromatography. In separate experiments, mice breathed 80 ppm NO for 1 h prior to cardiac I/R injury (induced by coronary arterial ligation for 1 h, followed by recovery). After sacrifice, the size of the myocardial infarction (MI) and the area at risk (AAR) were measured., Results: After NO inhalation, elevated nitroso/nitrosyl levels returned to baseline over the next 24 h, with distinct multi-phasic decay profiles in each compartment. S/N-nitroso compounds and NO-hemoglobin in blood decreased exponentially, but remained above baseline for up to 30min, whereas nitrate was elevated for up to 3hrs after discontinuing NO breathing. Hepatic S/N-nitroso species concentrations remained steady for 30min before dropping exponentially. Nitrate only rose in blood, liver and kidney; nitrite tended to be lower in all organs immediately after NO inhalation but fluctuated considerably in concentration thereafter. NO inhalation before myocardial ischemia decreased the ratio of MI/AAR by 30% vs controls (p = 0.002); only cardiac S-nitrosothiols and NO-hemes were elevated at time of reperfusion onset., Conclusions: Metabolites in blood do not reflect NO metabolite status of any organ. Although NO is rapidly inactivated by hemoglobin-mediated oxidation in the circulation, long-lived tissue metabolites may account for the myocardial preconditioning effects of inhaled NO. NO inhalation may afford similar protection in other organs., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2018
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15. Development of a portable mini-generator to safely produce nitric oxide for the treatment of infants with pulmonary hypertension.

Author

Yu B, Ferrari M, Schleifer G, Blaesi AH, Wepler M, Zapol WM, and Bloch DB

Subjects
Administration, Inhalation, Animals, Equipment Design, Female, Male, Metals isolation & purification, Nitric Oxide therapeutic use, Rabbits, Temperature, Ventricular Pressure drug effects, Calcium Hydroxide administration & dosage, Hypertension, Pulmonary drug therapy, Nitric Oxide administration & dosage, Respiratory Therapy instrumentation
Abstract

Objectives: To test the safety of a novel miniaturized device that produces nitric oxide (NO) from air by pulsed electrical discharge, and to demonstrate that the generated NO can be used to vasodilate the pulmonary vasculature in rabbits with chemically-induced pulmonary hypertension., Study Design: A miniature NO (mini-NO) generator was tested for its ability to produce therapeutic levels (20-80 parts per million (ppm)) of NO, while removing potentially toxic gases and metal particles. We studied healthy 6-month-old New Zealand rabbits weighing 3.4 ± 0.4 kg (mean ± SD, n = 8). Pulmonary hypertension was induced by chemically increasing right ventricular systolic pressure to 28-30 mmHg. The mini-NO generator was placed near the endotracheal tube. Production of NO was triggered by a pediatric airway flowmeter during the first 0.5 s of inspiration., Results: In rabbits with acute pulmonary hypertension, the mini-NO generator produced sufficient NO to induce pulmonary vasodilation. Potentially toxic nitrogen dioxide (NO 2 ) and ozone (O 3 ) were removed by the Ca(OH) 2 scavenger. Metallic particles, released from the electrodes by the electric plasma, were removed by a 0.22 μm filter. While producing 40 ppm NO, the mini-NO generator was cooled by a flow of air (70 ml/min) and the external temperature of the housing did not exceed 31 °C., Conclusions: The mini-NO generator safely produced therapeutic levels of NO from air. The mini-NO generator is an effective and economical approach to producing NO for treating neonatal pulmonary hypertension and will increase the accessibility and therapeutic uses of life-saving NO therapy worldwide., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2018
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16. Detection and removal of impurities in nitric oxide generated from air by pulsed electrical discharge.

Author

Yu B, Blaesi AH, Casey N, Raykhtsaum G, Zazzeron L, Jones R, Morrese A, Dobrynin D, Malhotra R, Bloch DB, Goldstein LE, and Zapol WM

Subjects
Administration, Inhalation, Air Filters, Air Pollutants analysis, Air Pollutants chemistry, Animals, Electrodes, Filtration, Iridium chemistry, Lung chemistry, Lung drug effects, Male, Metals, Heavy analysis, Metals, Heavy chemistry, Metals, Heavy isolation & purification, Mice, Mice, Inbred C57BL, Nitric Oxide adverse effects, Nitric Oxide chemistry, Temperature, Air Pollutants isolation & purification, Drug Contamination prevention & control, Nitric Oxide administration & dosage
Abstract

Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation without dilating the systemic circulation. However, the current NO/N 2 cylinder delivery system is cumbersome and expensive. We developed a lightweight, portable, and economical device to generate NO from air by pulsed electrical discharge. The objective of this study was to investigate and optimize the purity and safety of NO generated by this device. By using low temperature streamer discharges in the plasma generator, we produced therapeutic levels of NO with very low levels of nitrogen dioxide (NO 2 ) and ozone. Despite the low temperature, spark generation eroded the surface of the electrodes, contaminating the gas stream with metal particles. During prolonged NO generation there was gradual loss of the iridium high-voltage tip (-90 μg/day) and the platinum-nickel ground electrode (-55 μg/day). Metal particles released from the electrodes were trapped by a high-efficiency particulate air (HEPA) filter. Quadrupole mass spectroscopy measurements of effluent gas during plasma NO generation showed that a single HEPA filter removed all of the metal particles. Mice were exposed to breathing 50 parts per million of electrically generated NO in air for 28 days with only a scavenger and no HEPA filter; the mice did not develop pulmonary inflammation or structural changes and iridium and platinum particles were not detected in the lungs of these mice. In conclusion, an electric plasma generator produced therapeutic levels of NO from air; scavenging and filtration effectively eliminated metallic impurities from the effluent gas., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2016
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17. Hemoglobin infusion does not alter murine pulmonary vascular tone.

Author

Beloiartsev A, Baron DM, Yu B, Bloch KD, and Zapol WM

Subjects
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology, Analysis of Variance, Animals, Blood Pressure drug effects, Diabetes Mellitus, Experimental, Hypoxia, Lung chemistry, Lung metabolism, Male, Mice, Mice, Inbred C57BL, NG-Nitroarginine Methyl Ester metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Superoxides metabolism, Thoracotomy, Vasoconstrictor Agents pharmacology, Hemoglobins administration & dosage, Lung blood supply, Lung drug effects, Vascular Resistance drug effects, Vasoconstriction drug effects
Abstract

Plasma hemoglobin (Hb) scavenges endothelium-derived nitric oxide (NO), producing systemic and pulmonary vasoconstriction in many species. We hypothesized that i.v. administration of murine cell-free Hb would produce pulmonary vasoconstriction and enhance hypoxic pulmonary vasoconstriction (HPV) in mice. To assess the impact of plasma Hb on basal pulmonary vascular tone in anesthetized mice we measured left lung pulmonary vascular resistance (LPVRI) before and after infusion of Hb at thoracotomy. To confirm the findings obtained at thoracotomy, measurements of right ventricular systolic pressure (RVSP) and systemic arterial pressure (SAP) were obtained in closed-chest wild-type mice. To elucidate whether pretreatment with Hb augments HPV we assessed the increase in LPVRI before and during regional lung hypoxia produced by left mainstem bronchial occlusion (LMBO) in wild-type mice pretreated with Hb. Infusion of Hb increased SAP but did not change pulmonary arterial pressure (PAP), left lung pulmonary arterial flow (QLPA) or LPVRI in either wild-type or diabetic mice with endothelial dysfunction. Scavenging of NO by plasma Hb did not alter HPV in wild-type mice. Inhibition of NO synthase with l-NAME did not change the basal LPVRI, but augmented HPV during LMBO. Our data suggest that scavenging of NO by plasma Hb does not alter pulmonary vascular tone in mice. Therefore, generation of NO in the pulmonary circulation is unlikely to be responsible for the low basal pulmonary vascular tone of mice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Published
2013
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18. Nitric oxide regulates pulmonary vascular smooth muscle cell expression of the inducible cAMP early repressor gene.

Author

Steinbicker AU, Liu H, Jiramongkolchai K, Malhotra R, Choe EY, Busch CJ, Graveline AR, Kao SM, Nagasaka Y, Ichinose F, Buys ES, Brouckaert P, Zapol WM, and Bloch KD

Subjects
Animals, Cells, Cultured, Male, Mice, Mice, Inbred C57BL, Muscle, Smooth, Vascular cytology, Nucleic Acid Hybridization, Pulmonary Artery cytology, RNA, Messenger genetics, Rats, Reverse Transcriptase Polymerase Chain Reaction, Cyclic AMP Response Element Modulator genetics, Muscle, Smooth, Vascular metabolism, Nitric Oxide metabolism, Pulmonary Artery metabolism
Abstract

Nitric oxide (NO) regulates vascular smooth muscle cell (VSMC) structure and function, in part by activating soluble guanylate cyclase (sGC) to synthesize cGMP. The objective of this study was to further characterize the signaling mechanisms by which NO regulates VSMC gene expression using transcription profiling. DNA microarrays were hybridized with RNA extracted from rat pulmonary artery smooth muscle cells (RPaSMC) exposed to the NO donor compound, S-nitroso-glutathione (GSNO). Many of the genes, whose expression was induced by GSNO, contain a cAMP-response element (CRE), of which one encoded the inducible cAMP early repressor (ICER). sGC and cAMP-dependent protein kinase, but not cGMP-dependent protein kinase, were required for NO-mediated phosphorylation of CRE-binding protein (CREB) and induction of ICER gene expression. Expression of a dominant-negative CREB in RPaSMC prevented the NO-mediated induction of CRE-dependent gene transcription and ICER gene expression. Pre-treatment of RPaSMC with the intracellular calcium (Ca(2+)) chelator, BAPTA-AM, blocked the induction of ICER gene expression by GSNO. The store-operated Ca(2+) channel inhibitors, 2-ABP, and SKF-96365, reduced the GSNO-mediated increase in ICER mRNA levels, while 2-ABP did not inhibit GSNO-induced CREB phosphorylation. Our results suggest that induction of ICER gene expression by NO requires both CREB phosphorylation and Ca(2+) signaling. Transcription profiling of RPaSMC exposed to GSNO revealed important roles for sGC, PKA, CREB, and Ca(2+) in the regulation of gene expression by NO. The induction of ICER in GSNO-treated RPaSMC highlights a novel cross-talk mechanism between cGMP and cAMP signaling pathways., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Published
2011
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19. Handoffs causing patient harm: a survey of medical and surgical house staff.

Author

Kitch BT, Cooper JB, Zapol WM, Marder JE, Karson A, Hutter M, and Campbell EG

Subjects
Communication, Health Care Surveys, Massachusetts, Medical Errors, Quality of Health Care, Continuity of Patient Care, General Surgery, Medical Staff, Hospital, Patient Transfer
Abstract

Background: Communication lapses at the time of patient handoffs are believed to be common, and yet the frequency with which patients are harmed as a result of problematic handoffs is unknown. Resident physicians were surveyed about their handoffpractices and the frequency with which they perceive problems with handoffs lead to patient harm., Methods: A survey was conducted in 2006 of all resident physicians in internal medicine and general surgery at Massachusetts General Hospital (MGH) concerning the quality and effects of handoffs during their most recent inpatient rotations. Surveys were sent to 238 eligible residents; 161 responses were obtained (response rate, 67.6%)., Results: Fifty-nine percent of residents reported that one or more patients had been harmed during their most recent clinical rotation because of problematic handoffs, and 12% reported that this harm had been major. Overall quality of handoffs was reported to be fair or poor by 31% of residents. A minority of residents (26%) reported that handoffs usually or always took place in a quiet setting, and 37% reported that one or more interruptions during the receipt of handoffs occurred either most of the time or always., Discussion: Although handoffs have long been recognized as potentially hazardous, further scrutiny of handoffs has followed recent reports that handoffs are often marked by missing, incomplete, or inaccurate information and are associated with adverse events. In this study, reports of harm to patients from problematic handoffs were common among residents in internal medicine and general surgery. Many best-practice recommendations for handoffs are not observed, although the extent to which improvement of these practices could reduce patient harm is not known. MGH has recently launched a handoff-safety educational program, along with other interventions designed to improve the safety and effectiveness of handoffs, for its house staff and clinical leadership.

Published
2008
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20. Combined administration of intravenous dipyridamole and inhaled nitric oxide to assess reversibility of pulmonary arterial hypertension in potential cardiac transplant recipients.

Author

Lepore JJ, Dec GW, Zapol WM, Bloch KD, and Semigran MJ

Subjects
Administration, Inhalation, Adult, Aged, Blood Pressure drug effects, Drug Combinations, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Phosphodiesterase Inhibitors administration & dosage, Pulmonary Artery physiology, Dipyridamole administration & dosage, Heart Transplantation, Nitric Oxide administration & dosage, Vascular Resistance drug effects
Abstract

Background: Irreversible, severe pulmonary hypertension (PH) can produce right heart failure and early mortality after cardiac transplantation. We hypothesized that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the ability of inhaled nitric oxide (NO) to identify reversibility of PH., Methods: In 9 patients with congestive heart failure (CHF) and severe PH who were breathing 100% oxygen during right heart catheterization, we administered inhaled NO (80 ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus, with an infusion of 0.0375 mg/kg/min)., Results: Compared with breathing oxygen alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular resistance (PVR) (by 10 +/- 4% and 26 +/- 12% [mean +/- SEM], respectively; both p < 0.05). The combination of NO and dipyridamole reduced PVR (43 +/- 7%; p < 0.05) to a greater extent than did administration of NO alone, and increased the duration of pulmonary vasodilation produced by NO inhalation. Combined administration of inhaled NO and intravenous dipyridamole increased cardiac index (by 23 +/- 10%) and reduced SVR (by 19 +/- 6%, both p < 0.05) without changing systemic arterial pressure. NO inhalation reduced PVR to <200 dyne x s/cm5 in 3 of 7 patients who had a PVR of >200 dyne x s/cm5 when breathing oxygen alone, whereas the combination of NO and dipyridamole decreased PVR to <200 dyne.s/cm(5) in 2 additional patients., Conclusions: Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasodilator response to inhalation of NO alone is not observed.

Published
2005
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21. Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide.

Author

Lepore JJ, Maroo A, Bigatello LM, Dec GW, Zapol WM, Bloch KD, and Semigran MJ

Subjects
Adult, Bronchodilator Agents pharmacology, Cardiac Output drug effects, Drug Therapy, Combination, Female, Heart Failure physiopathology, Humans, Hypertension, Pulmonary physiopathology, Male, Middle Aged, Nitric Oxide pharmacology, Pulmonary Artery drug effects, Pulmonary Artery physiopathology, Purines, Sildenafil Citrate, Sulfones, Heart Failure drug therapy, Hemodynamics drug effects, Hypertension, Pulmonary drug therapy, Phosphodiesterase Inhibitors pharmacology, Piperazines pharmacology, Vasodilator Agents pharmacology
Abstract

Study Objectives: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH., Design: Single center, case series, pharmacohemodynamic study., Setting: Cardiac catheterization laboratory of a tertiary care academic teaching hospital., Patients: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH., Interventions: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization., Measurements and Results: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 +/- 5%, PVR by 12 +/- 5%, systemic vascular resistance (SVR) by 13 +/- 6%, and pulmonary capillary wedge pressure by 12 +/- 7%, and increased CI by 14 +/- 5% (all p < 0.05) [+/- SEM]. The combination of inhaled NO and sildenafil decreased PVR by 50 +/- 4%, decreased SVR by 24 +/- 3%, and increased CI by 30 +/- 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function., Conclusions: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH.

Published
2005
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