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1. Metrics of high cofluctuation and entropy to describe control of cardiac function in the stellate ganglion

Author

Nil Z Gurel, Koustubh B Sudarshan, Joseph Hadaya, Alex Karavos, Taro Temma, Yuichi Hori, J Andrew Armour, Guy Kember, and Olujimi A Ajijola

Subjects
sudden cardiac death, stellate ganglion, cardiac nervous system, cardiac control, neural population dynamics, neural recordings, Medicine, Science, Biology (General), QH301-705.5
Abstract

Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within the neurons of the stellate ganglion (SG) in the setting of heart failure (HF). A large proportion of SG neurons function as interneurons whose networking capabilities are largely unknown. Current therapies are limited to targeting sympathetic activity at the cardiac level or surgical interventions such as stellectomy, to treat HF. Future therapies that target the SG will require understanding of their networking capabilities to modify any pathological remodeling. We observe SG networking by examining cofluctuation and specificity of SG networked activity to cardiac cycle phases. We investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced HF and control subjects during extended in-vivo extracellular microelectrode recordings. We find that information processing and cardiac control in chronic HF by the SG, relative to controls, exhibits: (i) more frequent, short-lived, high magnitude cofluctuations, (ii) greater variation in neural specificity to cardiac cycles, and (iii) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude.

Published
2022
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2. Studying Cardiac Neural Network Dynamics: Challenges and Opportunities for Scientific Computing

Author

Nil Z. Gurel, Koustubh B. Sudarshan, Sharon Tam, Diana Ly, J. Andrew Armour, Guy Kember, and Olujimi A. Ajijola

Subjects
neurocardiology, sudden cardiac death (SCD), closed-loop control, cardiac nervous system, cardiac function, Physiology, QP1-981
Abstract

Neural control of the heart involves continuous modulation of cardiac mechanical and electrical activity to meet the organism’s demand for blood flow. The closed-loop control scheme consists of interconnected neural networks with central and peripheral components working cooperatively with each other. These components have evolved to cooperate control of various aspects of cardiac function, which produce measurable “functional” outputs such as heart rate and blood pressure. In this review, we will outline fundamental studies probing the cardiac neural control hierarchy. We will discuss how computational methods can guide improved experimental design and be used to probe how information is processed while closed-loop control is operational. These experimental designs generate large cardio-neural datasets that require sophisticated strategies for signal processing and time series analysis, while presenting the usual large-scale computational challenges surrounding data sharing and reproducibility. These challenges provide unique opportunities for the development and validation of novel techniques to enhance understanding of mechanisms of cardiac pathologies required for clinical implementation.

Published
2022
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3. Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.

Author

Guy Kember, Jeffrey L Ardell, Kalyanam Shivkumar, and J Andrew Armour

Subjects
Medicine, Science
Abstract

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

Published
2017
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4. Vagal nerve stimulation therapy: what is being stimulated?

Author

Guy Kember, Jeffrey L Ardell, John A Armour, and Mair Zamir

Subjects
Medicine, Science
Abstract

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Published
2014
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5. Metrics of high cofluctuation and entropy to describe control of cardiac function in the stellate ganglion

Author

Koustubh B Sudarshan, Nil Z Gurel, Joseph Hadaya, Alex Karavos, Taro Temma, Yuichi Hori, J Andrew Armour, Guy Kember, and Olujimi A Ajijola

Subjects
General Immunology and Microbiology, General Neuroscience, General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within the neurons of the stellate ganglion (SG) in the setting of heart failure. A large proportion of SG neurons function as interneurons whose networking capabilities are largely unknown. Current therapies are limited to targeting sympathetic activity at the cardiac level or surgical interventions such as stellectomy, to treat heart failure. Future therapies that target the stellate ganglion will require understanding of their networking capabilities to modify any pathological remodeling. We observe SG networking by examining cofluctuation and specificity of SG networked activity to cardiac cycle phases. We investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced heart failure and control subjects during extended in-vivo extracellular microelectrode recordings. We find that information processing and cardiac control in chronic heart failure by the SG, relative to controls, exhibits: i) more frequent, short-lived, high magnitude cofluctuations, ii) greater variation in neural specificity to cardiac cycles, and iii) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude.

Published
2022
Full Text
View/download PDF

7. Studying Cardiac Neural Network Dynamics: Challenges and Opportunities for Scientific Computing

Author

Nil Z. Gurel, Koustubh B. Sudarshan, Sharon Tam, Diana Ly, J. Andrew Armour, Guy Kember, and Olujimi A. Ajijola

Subjects
Physiology, Physiology (medical)
Abstract

Neural control of the heart involves continuous modulation of cardiac mechanical and electrical activity to meet the organism’s demand for blood flow. The closed-loop control scheme consists of interconnected neural networks with central and peripheral components working cooperatively with each other. These components have evolved to cooperate control of various aspects of cardiac function, which produce measurable “functional” outputs such as heart rate and blood pressure. In this review, we will outline fundamental studies probing the cardiac neural control hierarchy. We will discuss how computational methods can guide improved experimental design and be used to probe how information is processed while closed-loop control is operational. These experimental designs generate large cardio-neural datasets that require sophisticated strategies for signal processing and time series analysis, while presenting the usual large-scale computational challenges surrounding data sharing and reproducibility. These challenges provide unique opportunities for the development and validation of novel techniques to enhance understanding of mechanisms of cardiac pathologies required for clinical implementation.

Published
2021

8. Abstracts

Author

Cristina Hurtado, John Bradley, Andrew R. Burns, Keyvan Karkouti, Rob Anderson, Simon D. Abrahamson, C. David Mazer, O. R. Hung, L. Comeau, Joseph A. Fisher, Janet Tessler, Joshua Rucker, Alix Mathicu, Sara Murray-Foster, Chou Tz-Chong, Li Chi-Yuan, Takako Tsuda, Akihiko Tabuchi, Hiroshi Sasano, Masanobu Kiriyama, Akinori Okada, Junichiro Hayano, Akinori Takeuchi, Hirotada Katsuya, Claude P. Tousignant, Elizabeth Ling, Ramiro Arellano, N. Dowd, J. Karski, D. Cheng, J. Carroll-Munro, D. K. Rose, C. O. Mazer, M. M. Cohen, D. Wigglesworth, William P. S. McKay, Robert J. Teskey, Julio Militzer, Guy Kember, Travis Blanchet, Peter H. Gregson, Steven R. Howells, James A. Robblee, Terrance W. Breen, Laura Dierenfield, Tacie McNeil, Donna J. Nicholson, Stephen E. Kowalski, G. Andrew Hamilton, Michael P. Meyers, Carl Serrette, Peter C. Duke, Ingrid Custeau, Rend Martin, Sonia Larabée, Martine Pirlet, Madeleine Pilote, Jean-Pierre Tetrault, Ban C. H. Tsui, Sunil Gupta, Brendan Finucane, Mitchell J. Weisbrod, Vincent W. S. Chan, Z. Kaszas, C. Dragomir, M. R. Cohen, M. Gandhi, A. S. Clanachan, B. A. Finegan, Lisa Isaac, William M. Splinter, L. A. Hall, H. M. Gould, E. J. Rhine, Lyne Bergeron, Michel Girard, Pierre Drolet, Hong Hanh Le Truong, Carl Boucher, Daniel Vézina, Martin R. Lessard, Marie Gourdeau, Claude A. Trépanier, Theresa Yang, Alison Macarthur, P. Chouinard, F. Fugère, M. Ruel, Pekka Tarkkila, Marja Silvasti, Marjatta Tuominen, Nils Svartling, Per H. Rosenberg, David M. Bond, John F. Rudan, Michael A. Adams, Brian K. Tsang, Wanda Keahey, Lucia Gagliese, Marla Jackson, Paul Ritvo, Adarose Wowk, Alan N. Sandler, Joel Katz, J. G. Laffey, J. F. Boylan, Neal H. Badner, Wendy E. Komar, R. A. Cherry, S. M. Spadafora, R. J. Butler, Fiona McHardy, Joanne Fortier, Frances Chung, Scott Marshall, Ananthan Krishnathas, Jean Wong, Ewan Ritchie, Andrew Meikle, Nicole Avery, Janet van Vlymen, Joel L. Parlow, David Sinclair, Gabor Mezei, Fengling Jin, Andrew Norris, Tharini Ganeshram, Bernard A. MacLeod, Aliréza Azmudéh, Luigi G. Franciosi, Craig R. Ries, Stephan K. W. Schwarz, William PS McKay, Benjamin W. S. McKay, Pascal Meuret, Vincent Bonhomme, Gilles Plourde, Pierre Fiset, Stevens B. Backman, Alex Vesely, Leeor Sommer, Joel Greenwald, Elana Lavine, Steve Iscoe, George Volgyesi, Ludwik Fedorko, Joseph Fisher, Emilio B. Lobato, Cheri A. Sulek, Laurie K. Davies, Peter F. Gearen, François Bellemare, François Donati, Jacques Couture, Hwan S. Joo, Sunil Kapoor, Shahriar Shayan, Kenneth M. LeDez, Jim Au, John H. Tucker, Edwin B. Redmond, V. Gadag, Catherine Penney, Gregory M. T. Hare, Timothy D. G. Lee, Gregory M. Hirsch, Fan Yang, Eric Troncy, Gilbert Blaise, Yoshiyuki Naito, Shoji Arisawa, Masahiro Ide, Susumu Nakano, Kazuo Yamazaki, Takae Kawamura, Noriko Nara, Reiji Wakusawa, Katsuya Inada, Robert J. Hudson, Karanbir Singh, Gary A. Harding, Blair T. Henderson, Ian R. Thomson, Christopher G. Wherrett, Donald R. Miller, Alan A. Giachino, Michelle A. Turek, Kelly Rody, H. Vaghadia, V. Chan, S. Ganapathy, A. Lui, J. McKenna, K. Zimmer, William D. Regan, Ross G. Davidson, Krista Nevin, Sergio Escobedo, E. Mitmaker, M. J. Tessler, K. Kardash, S. J. Kleiman, M. Rossignol, L. Kahn, F. Baxter, A. Dauphin, C. Goldsmith, P. Jackson, J. McChesney, J. Miller, L. Takeuchi, E. Young, Kristine Klubien, Edith Bandi, Franco Carli, Kathleen Dattilo, Doris Tong, Mohit Bhandari, Louise Mazza, Linda Wykes, L. Z. Sommer, J. Rucker, A. Veseley, E. Levene, Y. Greenwald, G. Volgyesi, L. Fedorko, S. Iscoe, J. A. Fisher, Guo-Feng Tian, Andrew J. Baker, F. X. Reinders, A. J. Baker, R. J. Moulton, J. I. M. Brown, L. Schlichter, Laurence Van Tulder, Stéphane Carignan, Julie Prénovault, Jean-Paul Collet, Stan Shapiro, Jean-Gilles Guimond, Louis Blait, Thierry Ducruet, Martin Francœur, Marc Charbonneau, Guy Cousineau, Daniel R. Wong, Michele McCall, Fergus Walsh, Regina Kurian, Mary Keith, Michael J. Sole, Kursheed N. Jeejeebhoy, E. Whitten, P. H. Norman, J. A. Aucar, L. A. Coveler, Rodney M. Solgonick, Y. Bastien, Bruce Mazer, Koji Lihara, Beverley A. Orser, Michael Tymianski, Brendan T. Finucane, Nuzhat Zaman, Ibrahim Kashkari, Soheir Tawfik, Yun K. Tarn, Peter D. Slinger, Karen McRae, Timothy Winton, Alan N. Sandier, J. E. Zamora, Mary Jane Salpeter, Donglin Bai, John F. MacDonald, Kelly Mayson, Ed Gofton, Keith Chambers, Susan E. Belo, J. Colin Kay, Sean R. R. Hall, Louie Wang, Brian Milne, Chris Loomis, Zhi He, Wichai Wougchanapai, Ing K. Ho, John H. Eichhorn, Tangeng Ma, Wichai Wongchanapai, John H. Eicnhorn, Damian B. Murphy, M. B. Murphy, Steven B. Backman, Reuben D. Stein, Brian Collier, Canio Polosa, Chi-Yuan Li, Tz-Chong Chou, Jia-Yi Wang, John Fuller, Ronald Butler, Salvatore Spadafora, Neil Donen, Laurence Brownell, Sandy Shysh, Keith Carter, Chris Eagle, Isabella Devito, Stephen Halpern, J. Hugh Devitt, Doreen A. Yee, John L. deLacy, Donald C. Oxorn, Gary F. Morris, Raymond W. Yip, M. G. Gregoret-Quinn, R. F. Seal, LJ. Smith, A. B. Jones, C. Tang, B. J. Gallant, L. A. Nadwidny, Gerald V. Goresky, Tara Cowtan, Hilary S. Bridge, Carolyne J. Montgomery, Ross A. Kennedy, Pamela M. Merrick, M. Yamashita, K. Wada, Sylvie LeMay, Jean-François Hardy, Pamela Morgan, Steven Halpern, Jana Evers, P. Ronaldson, F. Dexter, Desmond Writer, Holly Muir, Romesh Shukla, Rob Nunn, John Scovil, Jeremy Pridham, Ola Rosaeg, Allan Sandier, Patricia Morley-Foster, Simon Lucy, Lesley-Ann Crone, Karen Zimmer, Deborah J. Wilson, Robert Heid, M. Joanne Douglas, Dan W. Rurak, Anna Fabrizi, Chantal T. Crochetière, Louise Roy, Edith Villeneuve, Louise Lortie, Sandra Katsiris, Barbara Leighton, Donna Wilson, Jean Kronberg, Leszek Swica, Janet Midgley, Robert Nunn, Bruce Smith, Michael E. Rooney, David C. Campbell, Celina M. Riben, Ray W. Yip, Jo MacDonell, and Tracey Levine

Subjects
Sevoflurane, Anesthesiology and Pain Medicine, Morphine, Total Knee Arthroplasty, Pulmonary Capillary Wedge Pressure, Ropivacaine, General Medicine, Article
Published
1998

9. Abstracts

Author

C. A. Botero, C. E. Smith, C. Holbrook, A. C. Pinchak, David Johnson, Dorothy Thomson, Taras Mycyk, M. Burbridge, Irvin Mayers, nR. W. M. Wahba, F. Belque, S. J. Kleiman, Steven Parker, Peter Cox, Helen Holtby, Lawrence Roy, Marc A. St-Amand, John M. Murkin, Donna Baird, Donal B. Downey, Alan H. Menkis, Fan Yang, Éric Troncy, Martin Francœur, Marc Charbonneau, Patrick Vinay, Gilbert Blaise, William M. Splinter, David J. Roberts, Elliot J. Rhine, Helen B. MacNeill, Craig W. Reid, William PS McKay, Miklavs Erjavec, Benjamin W. S. McKay, Peter H. Gregson, Travis Blanchet, Guy Kember, Josée Lavoie, Daniel Vischoff, Louise Cyrenne, Edith Villeneuve, Pierre Williot, A. K. Raghupathy, R. Haug, B. Punjabi, F. Ditzig, Howard Melnik, Michael J. Tessler, L. Jill Krasner, David M. Corda, Kal Solanki, A. Joseph Layon, T. James Gallagher, Daniel P. Stoltzfus, Shannon L. Rabuka, Carol A. Moote, Robert J. B. Chen, Doreen A. Yee, Ellen Harrington, Beverley A. Orser, D. Mitch Giffin, Kenneth W. Gow, P. Terry Phang, Keith R. Walley, C. Brian Warriner, Matthew H. Cohen, Andrew J. Klahsen, Deirdre O’Reilly, John McBride, Margaret Ballantyne, Blair D. Goranson, Scott Lang, William N. Dust, Jeff McKerrell, Guy Martin, René Martin, Daniel Martin, Philippe Valet, Jean-Pierre Tétrault, Caroline Dagenais, Martine Pirlet, Dominique Dansereau, Pedro D’Orléans-Justes, Agnès Jankowska, Yves Veillette, Angela L. Mathieson, Howard Intrater, Lionel Cruickshank, P. C. Duke, B. Y. Ong, Vincent Woo, Donna Schimnowski, Sharon Trosky, Linda Dalton, Ibrahim Zabani, Colin R. Chilvers, Himat Vaghadia, Pamela M. Merrick, Ibrahim Kashkari, Hossam Al-Oufi, D. Jolly, B. T. Finucane, Wolfgang Weyland, Ulrich Fritz, Heike Landmann, Ingrid Schumacher, Michael English, Dietrich Kettler, Catherine M. Duffy, Pirjo H. Manninen, Frances Chung, Shanthini Sundar, Emilio B. Lobato, Orlando Florete, Glenn B. Paige, Thierry Daloze, Daniel A. Chartrand, Denis St-Laurent, Gordon S. Fox, Murray L. Rice, D. John Doyle, George A. Volgyesi, Joseph A. Fisher, Arthur Slutsky, Igor Salazkin, Karen A. Brown, Pradeep Kulkarni, Bibiana Cujec, Randy McCuaig, Tom Hurst, David Antecol, François Bellemare, Jacques Couture, Manon Marchand, Peter McNeil, Orlando Hung, Lily M. Ho-Tai, J. Hugh Devitt, Alva G. Noel, Michael P. O’Donnell, Robert J. Greenhow, Frank W. Cervenko, Brian Milne, Mark D. Peterson, Ian R. Thomson, Robert J. Hudson, Morley Rosenbloom, Michael Moon, Jitender Sareen, H. Locke Bingham, Steven B. Backman, Reuben D. Stein, C. Polosa, Michael Tessler, Salvatore M. Spadafora, John G. Fuller, Lisa Kim, Keyvan Karkouti, D. Keith Rose, Lorraine E. Ferris, DK Rose, MM Cohen, F. E. Ralley, B. DeVarennes, M. Robitaille, Norman Searle, Raymond Martineau, Peter Conzen, A. Al-Hasani, Tom Ebert, Michael Muzi, Jean-François Hardy, Sylvain Bélisle, André Couturier, Danielle Robitaille, Micheline Roy, Lyne Gagnon, Elisabeth J. Avraamides, P. J. Dryden, J. P. O’Connor, W. R. E. Jamieson, I. Reid, D. Ansley, H. Sadeghi, L. H. Burr, A. I. Munro, P. M. Merrick, Mark Benaroia, Andrew Baker, C. David Mazer, Lee Errett, Luc Frenette, Jerry Cox, Donna Kerns, Steve Pearce, David Mark, Paul McDonagh, Lulz DeLlma, Howard Nathan, Jean-Yves Dupuls, J.Earl Wynands, G. C. Moudgil, J. G. Johnson, G. M. Moudgil, Richard I. Hall, Connie MacLaren, M. J. Ali, M. Ballantyne, D. Norris, Stephen D. Beed, Eugene A. Menard, Leon P. Noel, Gary G. Bonn, William Clarke, H. Marion Gould, Leslie E. Hall, Philippe Bernard, Juan Bass, Ramona A. Kearney, Cheryl A. Mack, Lucy M. Entwistle, Joan C. Bevan, Andrew J. Macnab, Guy Veall, Colin Marsland, Craig R. Ries, Shahnaz K. Hamid, Ian R. Selby, Nancy Sikich, Elizabeth Hsu, Patricia McCarthy, Ching-Yue Yang, Wun-Chin Wu, Jiunn-Jye Huang, Shyu-Yin Chen, Hsiang-Ning Luk, Chok-Yung Chai, Gina K. Lafreniere, Donald G. Brunet, Joel L. Parlow, Hossam El-Beheiry, Aviv Ouanounou, Mary Morris, Peter Carlen, Pamela J. Morgan, Roger Chapados, Marlene Gauthier, John W. D. Knox, Jacques LeLorier, Roddy Lin, Keith Rose, Bernadette Garvey, Robert McBrobm, L. C. McAdam, J. F. MacDonald, B. A. Orser, Georgios koutsoukos, Susan Belo, Christopher A. Chin, Brendan O’Hare, Jerrold Lerman, Junko Endo, Arthur E. Schwartz, Oktavijan Minanov, J. Gilbert Stone, David C. Adams, Aqeel A. Sandhu, Mark E. Pearson, William L. Young, Robert E. Michler, Ernest Cutz, Matt M. Kurrek, Marsha M. Cohen, Kevin Fish, Pamela Fish, Patricia Murphy, Donald Fung, Alva Noel, John-Paul Szalai, Ari Robicsek, Joshua Rucker, Joshua Kruger, Mark Slutsky, Leeor Sommer, Jeff Silverman, Jodi Dickstein, Viren Naik, Douglas J. Hemphill, Regina Kurian, Khursheed N. Jeejeebhoy, Osama A. Alahdal, N. H. Badner, W. E. Komar, R. Bhandari, R. Craen, D. Cuillerier, W. B. Dobkowski, M. H. Smith, A. N. Vannelli, R. B. Bourne, C. H. Rorabeck, J. A. Doyle, Antoinette Corvo, Richard M. Wahba, Nathalie Scheffer, John Y. C. Tsang, Brad A. Brush, N. Q. N’Guyen, C. Orain, S. Tougui, G. Lavenac, D. Milon, Ewan D. Ritchie, Doris Tong, Andrew Norris, Anthony Miniaci, Santhira D. Vairavanathan, Timothy FitzPatrick, Mark Stafford-Smith, Ken Kardash, Toula Trihas, Simcha J. Kleiman, Michel Rossignol, Dominique Bérard, Brent Martel, J. P. Tétrault, Peter G. Lunt, Dennis W. Coombs, Stephen Halpern, Elizabeth A. Peter, Patricia Janssen, Jill Mahy, M. Joanne Douglas, Caroline S. Grange, Timothy J. Adams, Louis Wadsworth, Holly Muir, Romesh Shukla, Desmond Writer, Richard McLaren, Robert Liston, Don Paetkau, Bill Y. Ong, Ron Segstro, Judy Littleford, Cristina Hurtado, Ananthan Krishnathas, Marcelo Lannes, Joanne Fortier, Jun Su, Rubini Jeganathan, and Suzanne Vaillancourt

Subjects
Anesthesiology and Pain Medicine, General Medicine
Published
1996
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