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1. Pulmonary Vascular Endothelial Responses are Differentially Modulated After Cardiopulmonary Bypass

Author

Daniel Nyhan, Brett A. Simon, Nicholas A. Flavahan, Mariesa Hales, Sean Gaine, Paul Zanaboni, and Dan E. Berkowitz

Subjects
Male, medicine.medical_specialty, Time Factors, Endothelium, Vasodilator Agents, Bradykinin, Vasodilation, In Vitro Techniques, Pulmonary Artery, Nitric Oxide, Muscle, Smooth, Vascular, law.invention, Phenylephrine, chemistry.chemical_compound, Dogs, law, Isometric Contraction, Internal medicine, medicine, Cardiopulmonary bypass, Animals, Vasoconstrictor Agents, Drug Interactions, Lung, Pharmacology, Cardiopulmonary Bypass, Dose-Response Relationship, Drug, business.industry, Acetylcholine, surgical procedures, operative, medicine.anatomical_structure, chemistry, Anesthesia, Circulatory system, Cardiology, Endothelium, Vascular, Cardiology and Cardiovascular Medicine, business, Muscle Contraction, circulatory and respiratory physiology, Blood vessel, medicine.drug
Abstract

Summary: The aim of this study was to characterize the mechanisms underlying pulmonary vascular dysfunction after cardiopulmonary bypass (CPB) by examining responses of isolated pulmonary arteries to selective endothelium-dependent and -independent activators in control and post-CPB dogs. Adult male mongrel dogs were placed on closed-chest, hypothermic CPB for 2.5 h, and then allowed to recover. Anatomically matched pulmonary arterial rings were isolated and suspended for isometric tension recording. Contractile responses to the α1-adrenergic agonist phenylephrine were similar in endothelium-containing arteries from control and CPB animals. Endothelium denudation increased contractions to phenylephrine to a similar extent in both groups. Endothelium-dependent relaxation to acetylcholine was decreased 4 days after CPB compared with controls. In contrast to acetylcholine, endothelium-dependent relaxation to bradykinin or to A23187 were not impaired 4 days after CPB. Inhibition of nitric oxide synthase (NOS) with L-NAME depressed the response to acetylcholine in control vessels, confirming that a component of the response to acetylcholine was nitric oxide (NO) dependent. At lower concentrations of acetylcholine, this component of the response was abolished after CPB. The residual relaxation evoked by acetylcholine in the presence of L-NAME also was impaired in CPB compared with control arteries. This suggests that the CPB-induced impairment of acetylcholine-evoked relaxation may not involve both an NO-mediated and an NO-independent component. L-NAME depressed the response to bradykinin to a similar degree in control and CPB arteries. Vascular smooth-muscle dilatation to the NO donor, SIN-1, or to the K+ATP-channel opener, cromakalim, were similar in endothelium-denuded arteries from CPB and control animals. These results suggest that CPB causes a selective impairment in endothelial dilator function without changing the vascular smooth-muscle response to vasodilator or vasoconstrictor stimuli.

Published
1999

3. Contributors

Author

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

Published
2011

4. Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass

Author

Kirk J. Fleischer, Kenton J. Zehr, Elaine E. Tseng, Paul Zanaboni, Daniel Nyhan, Brett A. Simon, and Paul A. Murray

Subjects
Male, Nitroprusside, Pulmonary Circulation, Endothelium, Physiology, Vasodilator Agents, Bradykinin, law.invention, Thromboxane A2, Animal model, Dogs, law, Physiology (medical), medicine, Cardiopulmonary bypass, Animals, Vasoconstrictor Agents, Postoperative Period, Endothelial dysfunction, Coronary Artery Bypass, Endothelium dependent vasodilation, business.industry, medicine.disease, Acetylcholine, Prostaglandin Endoperoxides, Synthetic, Vasodilation, Fleischer, surgical procedures, operative, medicine.anatomical_structure, Circulacion extracorporea, Anesthesia, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Blood Vessels, Endothelium, Vascular, business, circulatory and respiratory physiology
Abstract

Zanaboni, Paul, Paul A. Murray, Brett A. Simon, Kenton Zehr, Kirk Fleischer, Elaine Tseng, and Daniel P. Nyhan. Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass. J. Appl. Physiol. 82(6): 1776–1784, 1997.—It has previously been demonstrated that cardiopulmonary bypass (CPB) causes prolonged pulmonary vascular hyperreactivity (D. P. Nyhan, J. M. Redmond, A. M. Gillinov, K. Nishiwaki, and P. A. Murray. J. Appl. Physiol. 77: 1584–1590, 1994). This study investigated the effects of CPB on endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (sodium nitroprusside) pulmonary vasodilation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q˙) plots were generated in conscious dogs before CPB and again in the same animals 3–4 days post-CPB. The dose of U-46619 used to acutely preconstrict the pulmonary circulation to similar levels pre- and post-CPB was decreased (0.13 ± 0.01 vs. 0.10 ± 0.01 mg ⋅ kg−1 ⋅ min−1, P < 0.01) after CPB. Acetylcholine, bradykinin, and sodium nitroprusside all caused dose-dependent pulmonary vasodilation pre-CPB. The pulmonary vasodilator response to acetylcholine was completely abolished post-CPB. For example, at left pulmonary blood flow of 80 ml ⋅ kg−1 ⋅ min−1acetylcholine (10 μg ⋅ kg−1 ⋅ min−1) resulted in 72 ± 15% reversal ( P< 0.01) of U-46619 preconstriction pre-CPB but caused no change post-CPB. However, the responses to bradykinin and sodium nitroprusside were unchanged post-CPB. The impaired pulmonary vasodilator response to acetylcholine, but not to bradykinin, suggests a selective endothelial defect post-CPB. The normal response to sodium nitroprusside indicates that cGMP-mediated vasodilation is unchanged post-CPB.

Published
1997

5. Protein Kinase C in the Developing Rat Liver, Heart and Brain

Author

Paul Zanaboni, John Deguire, and Akihiko Noguchi

Subjects
Male, medicine.medical_specialty, Gestational Age, Biology, Chromatography, DEAE-Cellulose, Fetal Heart, Pregnancy, Internal medicine, medicine, Animals, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Protein kinase A, Protein Kinase C, Protein kinase C, Vasopressin receptor, Acetylcholine receptor, Fetus, Myocardium, Age Factors, Brain, Rats, Inbred Strains, Enzyme assay, Rats, Cytosol, Endocrinology, Liver, Hormone receptor, biology.protein, Female, Protein Kinases
Abstract

Ontogenic changes of protein kinase C in the rat liver, heart and cerebrum were examined from 17-day gestation until adult. Cerebral protein kinase C activity was 19 times less at 17-day fetal as compared to 15-day postnatum or older rats. The enzyme activity in the heart was generally higher in the neonatal period than the adult, but was not correlated with the previously reported alpha 1-adrenergic and cholinergic receptor ontogeny. Likewise in the liver, the enzyme activity was not correlated with previously reported alpha 1-adrenergic and vasopressin receptor ontogeny. No correlation between protein kinase C and cyclic AMP-dependent protein kinase activities was found among these tissues. The enzyme distribution expressed by a cytosol/particulate ratio of 0.72, 2.41 and 0.64 in the liver, heart and brain, respectively, in 20-day fetus was similar to adult values. We conclude that there is a discrete ontogenic pattern of protein kinase C in each organ and it does not seem to be correlated with the ontogenic pattern of hormone receptors which relate to phosphatidylinositol breakdown. The precise role of protein kinase C in relationship to growth and differentiation needs to be further investigated.

Published
1988

6. 297 PROTEIN KINASE C (PK-C) IN THE DEVELOPING RAT LIVER AND HEART

Author

John Deguire, Aklhiko Noguchi, and Paul Zanaboni

Subjects
medicine.medical_specialty, MAP kinase kinase kinase, Cyclin-dependent kinase 2, Biology, Mitogen-activated protein kinase kinase, MAP2K7, Cell biology, Endocrinology, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, biology.protein, Cyclin-dependent kinase 9, ASK1, Protein kinase A, Protein kinase C
Abstract

Ca dependent, phospholipid regulated protein kinase (PK-C) serves a crucial role for receptor activation by substances such as α-adrenergic agonists which stimulate phosphatidylinositol breakdown. Ontogeny of α1-receptors is known to be organ specific and distinct from β-receptors. To assess receptor-protein kinase relationship, ontogeny of PK-C and cAMP dependent protein kinase (PK-A) activities were compared to cytosol from rat liver and heart: Cytosol/particulate ratio of PK-C at 21d fetus were 0.72 & 2.41 for liver and heart and similar to adult. DEAE cellulose column separation of PK-C showed a major and a minor peak, & the minor peak was Ca and phosphatidylserine independent in liver and heart. This pattern did not change with age qualitatively. We conclude that PK-C activity is higher perinatally, its subcellular distribution does not seem to change with age, and it is not correlated with PK-A activity or previously reported α1-receptor density in these organs. We speculate that PK-C is not rate limiting in the receptor activation perinatally.

Published
1985

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