17 results on '"Cohen, Ira S"'
Search Results
2. Contributors
- Author
-
Aagaard, Philip, primary, Abrams, Dominic James, additional, Abriel, Hugues, additional, Adkisson, Wayne O., additional, Agullo-Pascual, Esperanza, additional, Alvarado, Francisco J., additional, Amin, Ahmad S., additional, Antzelevitch, Charles, additional, Anumonwo, Justus M.B., additional, Armaganijan, Luciana, additional, Arya, Arash, additional, Asirvatham, Samuel, additional, Atienza, Felipe, additional, Backx, Peter H., additional, Ballou, Lisa M., additional, Balse, Elise, additional, Balulad, Sujata, additional, Barbuti, Andrea, additional, Bardy, Gust H., additional, Bassil, Guillaume, additional, Benditt, David G., additional, Berenfeld, Omer, additional, Bers, Donald M., additional, Binah, Ofer, additional, Bogun, Frank, additional, Bongianino, Rossana, additional, Boyle, Noel G., additional, Boyle, Patrick M., additional, Breithardt, Günter, additional, Brini, Marisa, additional, Brink, Peter R., additional, Brugada, Pedro, additional, Buch, Eric, additional, Bukauskas, Feliksas F., additional, Calkins, Hugh, additional, Callans, David J., additional, Caples, Sean M., additional, Carafoli, Ernesto, additional, Catterall, William A., additional, Cerrone, Marina, additional, Chaumeil, Arnaud, additional, Chen, Caressa, additional, Chen, Lan S., additional, Chen, Peng-Sheng, additional, Cheng, Jianding, additional, Chiamvimonvat, Nipavan, additional, Christini, David J., additional, Chugh, Aman, additional, Climent, Andreu M., additional, Cohen, Ira S., additional, Connolly, Stuart J., additional, Cooper, Lebron, additional, Crespo, Eric M., additional, Crotti, Lia, additional, Csepe, Thomas A., additional, Cuoco, Frank, additional, Curtis, Anne B., additional, Damiano, Ralph J., additional, Darbar, Dawood, additional, Das, Mithilesh K., additional, d’Avila, Andre, additional, Delmar, Mario, additional, Delpón, Eva, additional, Denegri, Marco, additional, Denis, Arnaud, additional, Derval, Nicolas, additional, Deschênes, Isabelle, additional, Deshmukh, Abhishek, additional, Di Biase, Luigi, additional, Dickfeld, Timm M., additional, Dierckx, Hans, additional, Dinov, Borislav, additional, Dixit, Sanjay, additional, Dobrev, Dobromir, additional, Dubois, Remi, additional, Eckardt, Lars, additional, Edwards, Andrew G., additional, Ellenbogen, Kenneth A., additional, Ellinor, Patrick T., additional, Estes, N.A. Mark, additional, Fabritz, Larissa, additional, Fedorov, Vadim V., additional, Fernandez, Antonio B., additional, Teijeira Fernández, Elvis, additional, Filgueiras-Rama, David, additional, Fishbein, Michael C., additional, Fishman, Glenn I., additional, Frankel, David S., additional, Friedman, Paul, additional, Frontera, Antonio, additional, Gami, Apoor S., additional, Garabelli, Paul, additional, George, Alfred L., additional, Gerstenfeld, Edward P., additional, Gizurarson, Sigfus, additional, Gold, Michael R., additional, Goldberger, Jeffrey J., additional, Grace, Andrew, additional, Grassi, Guido, additional, Greenfield, Ruth Ann, additional, Gross, Wendy L., additional, Grubb, Blair P., additional, Guillem, María S., additional, Györke, Sándor, additional, Haïssaguerre, Michel, additional, Hake, Johan, additional, Halperin, Henry R., additional, Hansen, Brian J., additional, Hatem, Stéphane, additional, Hayes, David L., additional, Heijman, Jordi, additional, Herron, Todd J., additional, Hindricks, Gerhard, additional, Hocini, Mélèze, additional, Hohnloser, Stefan H., additional, Holmes, David R., additional, Hoshijima, Masahiko, additional, Hund, Thomas J., additional, Hutchinson, Mathew D., additional, Ilkhanoff, Leonard, additional, Ingles, Jodie, additional, Ip, James E., additional, Jackman, Warren M., additional, Jackson, Nicholas, additional, Jaïs, Pierre, additional, Jalife, José, additional, Jhun, Bong Sook, additional, John, Roy M., additional, Jongbloed, Monique, additional, Jordaens, Luc, additional, Kalman, Jonathan M., additional, Kamp, Timothy J., additional, Kanj, Mohamed H., additional, Kapa, Suraj, additional, Karabin, Beverly, additional, Karakikes, Ioannis, additional, Katritsis, Demosthenes G., additional, Kaur, Kuljeet, additional, Kirchhof, Paulus, additional, Kléber, André G., additional, Klein, George J., additional, Kohl, Peter, additional, Koneru, Jayanthi N., additional, Koruth, Jacob S., additional, Krahn, Andrew D., additional, Krogh-Madsen, Trine, additional, Kuck, Karl Heinz, additional, Kumar, Saurabh, additional, Kushnir, Alexander, additional, Lakdawala, Neal K., additional, Laksman, Zachary W.M., additional, Latchamsetty, Rakesh, additional, Lau, Dennis H., additional, Lerman, Bruce B., additional, Lin, Richard Z., additional, Lin, Shien-Fong, additional, Link, Mark S., additional, Liu, Bin, additional, Liu, Christopher F., additional, Lockwood, Deborah J., additional, Lopatin, Anatoli N., additional, Lubitz, Steven A., additional, Mahajan, Rajiv, additional, Makielski, Jonathan C., additional, Malik, Marek, additional, Marchlinski, Francis E., additional, Markowitz, Steven M., additional, Maron, Barry J., additional, Maron, Martin S., additional, Marx, Steven O., additional, Massé, Stéphane, additional, McCulloch, Andrew D., additional, McKelvie-Sebileau, Pippa, additional, Melby, Spencer J., additional, Metzner, Andreas, additional, Michailova, Anushka P., additional, Michaud, Gregory F., additional, Miller, John M., additional, Mishra, Jyotsna, additional, Mitrani, Raul D., additional, Mohler, Peter J., additional, Morady, Fred, additional, Myerburg, Robert J., additional, Nakagawa, Hiroshi, additional, Nalliah, Chrishan Joseph, additional, Nanthakumar, Kumaraswamy, additional, Napolitano, Carlo, additional, Narayan, Sanjiv M., additional, Natale, Andrea, additional, Nattel, Stanley, additional, Nazarian, Saman, additional, Nguyen, Thao P., additional, Nogami, Akihiko, additional, Noujaim, Sami F., additional, Nubret Le Coniat, Karine, additional, Olshansky, Brian, additional, O-Uchi, Jin, additional, Oudit, Gavin Y., additional, Ouyang, Feifan, additional, Ozcan, Cevher, additional, Packer, Douglas L., additional, Pandit, Sandeep V., additional, Panfilov, Alexander V., additional, Park, David S., additional, Patocskai, Bence, additional, Pauza, Dainius H., additional, Pauziene, Neringa, additional, Piccini, Jonathan P., additional, Pitt, Geoffrey S., additional, Po, Sunny S., additional, Prasad, Abhiram, additional, Priori, Silvia G., additional, Radwański, Przemysław B., additional, Rappel, Wouter-Jan, additional, Reiser, Michelle, additional, Restrepo, Alejandro Jimenez, additional, Robinson, Richard B., additional, Roden, Dan M., additional, Rosen, Michael R., additional, Rosso, Raphael, additional, Rudy, Yoram, additional, Rysevaite-Kyguoliene, Kristina, additional, Sabbah, Hani N., additional, Sacher, Frederic, additional, Sachse, Frank B., additional, Saguner, Ardan M., additional, Sanders, Prashanthan, additional, Sanguinetti, Michael C., additional, Santangeli, Pasquale, additional, Sarraf, Mohammad, additional, Satin, Jonathan, additional, Schalij, Martin Jan, additional, Scherlag, Benjamin J., additional, Schill, Matthew R., additional, Schleifer, J. William, additional, Schuessler, Richard B., additional, Schwartz, Peter J., additional, Seeger, Timon, additional, Semsarian, Christopher, additional, Seravalle, Gino, additional, Shah, Ashok J., additional, Shaw, Robin M., additional, Shen, Mark J., additional, Shen, Win–Kuang, additional, Sheu, Shey-Shing, additional, Shivkumar, Kalyanam, additional, Silva, Jennifer N.A., additional, Skanes, Allan C., additional, Soejima, Kyoko, additional, Somers, Virend K., additional, Sorajja, Dan, additional, Stavrakis, Stavros, additional, Steinberg, Christian, additional, Stevenson, Lynne Warner, additional, Stevenson, William G., additional, Sweeney, Michael O., additional, Swerdlow, Charles, additional, Takigawa, Masateru, additional, Tamargo, Juan, additional, Tandri, Harikrishna, additional, Tedrow, Usha B., additional, Thompson, Nathaniel, additional, Thompson, Paul D., additional, Tomaselli, Gordon F., additional, Towbin, Jeffrey A., additional, Trayanova, Natalia A., additional, Tristani-Firouzi, Martin, additional, Tseng, Zian H., additional, Ueda, Akiko, additional, Valdivia, Héctor H., additional, Valiunas, Virginijus, additional, van der Werf, Christian, additional, Van Hare, George F., additional, Vidmar, David, additional, Viskin, Sami, additional, Voigt, Niels, additional, Walsh, Edward P., additional, Wang, Paul J., additional, Wehrens, Xander H.T., additional, Weiss, Mark S., additional, Wilde, Arthur A.M., additional, Wilkoff, Bruce L., additional, Woo, Y. Joseph, additional, Wu, Joseph C., additional, Yee, Raymond, additional, Zaman, Junaid A.B., additional, Zarzoso, Manuel, additional, Zeitler, Emily P., additional, Zeppenfeld, Katja, additional, Zghaib, Tarek, additional, Zhang, Xiao-Dong, additional, and Zipes, Douglas P., additional
- Published
- 2018
- Full Text
- View/download PDF
3. Inhibition of Phosphoinositide 3-Kinase and Acquired Long QT Syndrome
- Author
-
Ballou, Lisa M., primary, Lin, Richard Z., additional, and Cohen, Ira S., additional
- Published
- 2018
- Full Text
- View/download PDF
4. Optogenetic Control of Heart Muscle
- Author
-
Entcheva, Emilia, primary and Cohen, Ira S., additional
- Published
- 2014
- Full Text
- View/download PDF
5. Contributors
- Author
-
Abriel, Hugues, primary, Adkisson, Wayne O., additional, Agullo-Pascual, Esperanza, additional, Ajijola, Olujimi A., additional, Al-Ahmad, Amin, additional, Alli, Oluseun, additional, Altman, Robert K., additional, Anter, Elad, additional, Antzelevitch, Charles, additional, Anumonwo, Justus M.B., additional, Armaganijan, Luciana, additional, Ashikaga, Hiroshi, additional, Atienza, Felipe, additional, Avula, Uma Mahesh R., additional, Backx, Peter H., additional, Balse, Elise, additional, Barrett, Conor D., additional, Benditt, David G., additional, Berenfeld, Omer, additional, Bers, Donald M., additional, Berul, Charles I., additional, Blank, A. Christian, additional, Bloise, Raffaella, additional, Bogun, Frank Matthias, additional, Borggrefe, Martin, additional, Boyle, Noel G., additional, Breithardt, Günter, additional, Brini, Marisa, additional, Brink, Peter R., additional, Brugada, Josep, additional, Brugada, Pau, additional, Brugada, Pedro, additional, Brugada, Ramon, additional, Brugada, Victoria, additional, Buch, Eric, additional, Bukauskas, Feliksas F., additional, Burkhardt, J. David, additional, Bursac, Nenad, additional, Calkins, Hugh, additional, Callans, David J., additional, Campuzano, Oscar, additional, Caples, Sean M., additional, Carafoli, Ernesto, additional, Castellanos, Augustin, additional, Catterall, William, additional, Cerrone, Marina, additional, Chen, Lan S., additional, Chen, Lei, additional, Chen, Peng-Sheng, additional, Chin, Ashley, additional, Chugh, Aman, additional, Cohen, Ira S., additional, Connolly, Stuart J., additional, Constantino, Jason, additional, Crotti, Lia, additional, Cuoco, Frank A., additional, Curtis, Anne B., additional, Damiano, Ralph J., additional, Darbar, Dawood, additional, Das, Mithilesh K., additional, Delmar, Mario, additional, Delpón, Eva, additional, Di Biase, Luigi, additional, Dixit, Sanjay, additional, Dobrev, Dobromir, additional, Dosdall, Derek J., additional, Dyer, John W., additional, Eckardt, Lars, additional, Edwards, Andrew G., additional, Efimov, Igor R., additional, Ellenbogen, Kenneth A., additional, Ellinor, Patrick T., additional, Entcheva, Emilia, additional, Estes, N.A. Mark, additional, Fischmeister, Rodolphe, additional, Fisher, John D., additional, Fishman, Glenn I., additional, Frankel, David S., additional, Franz, Michael R., additional, Friedman, Paul A., additional, Froelicher, Victor F., additional, Gami, Apoor S., additional, George, Alfred L., additional, Gerstenfeld, Edward P., additional, Gold, Michael R., additional, Goldberger, Jeffrey J., additional, Grandi, Eleonora, additional, Gray, Richard A., additional, Groh, William J., additional, Grubb, Blair P., additional, Haissaguerre, Michel, additional, Hake, Johan, additional, Halperin, Henry R., additional, Harris, Louise, additional, Hatem, Stéphane, additional, Hayes, David L., additional, Hocini, Meleze, additional, Hohnloser, Stefan H., additional, Holmes, David Richard, additional, Hoshijima, Masahiko, additional, Hu, Yuxuan, additional, Hund, Thomas J., additional, Hutchinson, Mathew D., additional, Hwang, Hye Jin, additional, Ideker, Raymond E., additional, Ilkhanoff, Leonard, additional, Ingles, Jodie, additional, Jackman, Warren M., additional, Jais, Pierre, additional, Jalife, José, additional, Jhun, Bong Sook, additional, John, Roy M., additional, Jongbloed, Monique, additional, Josephson, Mark E., additional, Kadish, Alan H., additional, Kalifa, Jérôme, additional, Kalman, Jonathan M., additional, Kamp, Timothy J., additional, Kanj, Mohamed Hani, additional, Karabin, Beverly, additional, Kass, Robert S., additional, Katritsis, Demosthenes G., additional, Kaur, Kuljeet, additional, Kim, Jong J., additional, Kirchhof, Paulus, additional, Kléber, André G., additional, Klein, George J., additional, Kohl, Peter, additional, Kolandaivelu, Aravindan, additional, Krahn, Andrew D., additional, Krumerman, Andrew, additional, Kumar, Saurabh, additional, Kuck, Karl-Heinz, additional, Lakatta, Edward G., additional, Latchamsetty, Rakesh, additional, Lau, Dennis H., additional, Lerman, Bruce B., additional, Leroy, Jérôme, additional, Lewis, William R., additional, Lin, Shien-Fong, additional, Link, Mark S., additional, Liu, Christopher F., additional, Lockwood, Deborah J., additional, Loh, Peter, additional, Lopatin, Anatoli N., additional, Lopshire, John C., additional, Lubitz, Steven A., additional, Madias, Christopher, additional, Mahajan, Aman, additional, Makielski, Jonathan C., additional, Malik, Marek, additional, Maltsev, Victor A., additional, Marchlinski, Francis E., additional, Marelli, Ariane J., additional, Markowitz, Steven M., additional, Maron, Barry J., additional, Martens, Jeffrey R., additional, Marx, Steven O., additional, McCulloch, Andrew D., additional, Metzner, Andreas, additional, Michailova, Anuska P., additional, Miller, John Michael, additional, Milstein, Michelle Lynne, additional, Mohler, Peter, additional, Morady, Fred, additional, Myerburg, Robert J., additional, Nakagawa, Hiroshi, additional, Napolitano, Carlo, additional, Narayan, Sanjiv M., additional, Natale, Andrea, additional, Nattel, Stanley, additional, Nazarian, Saman, additional, Nerbonne, Jeanne M., additional, Ng, Fu Siong, additional, Nogami, Akihiko, additional, Noujaim, Sami F., additional, Olshansky, Brian, additional, Oral, Hakan, additional, O-Uchi, Jin, additional, Ouyang, Feifan, additional, Ozcan, Cevher, additional, Packer, Douglas L., additional, Pahlm, Olle, additional, Pandit, Sandeep V., additional, Park, David S., additional, Pitt, Geoffrey S., additional, Po, Sunny S., additional, Priori, Silvia G., additional, Rappel, Wouter-Jan, additional, Reddy, Vivek Y., additional, Robertson, Jason O., additional, Robinson, Richard B., additional, Roden, Dan M., additional, Rose, Robert A., additional, Rosen, Michael R., additional, Rosso, Raphael, additional, Rudy, Yoram, additional, Ruskin, Jeremy N., additional, Sabbah, Hani N., additional, Sachse, Frank B., additional, Saint, Lindsey L., additional, Saiz, Javier, additional, Sánchez-Chapula, José A., additional, Sanders, Prashanthan, additional, Sanguinetti, Michael C., additional, Santangeli, Pasquale, additional, Sarquella-Brugada, Georgia, additional, Satin, Jonathan, additional, Schalij, Martin Jan, additional, Scherlag, Benjamin J., additional, Schimpf, Rainer, additional, Schmidt, Georg, additional, Schwartz, Peter J., additional, Semsarian, Christopher, additional, Shah, Ashok J., additional, Shaw, Robin, additional, Sheu, Shey Shing, additional, Shivkumar, Kalyanam, additional, Skanes, Allan C., additional, Somers, Virend K., additional, Stambler, Bruce S., additional, Stein, Adam B., additional, Stevenson, Lynne Warner, additional, Stevenson, William G., additional, Sun, Jian, additional, Sutton, Richard, additional, Sweeney, Michael O., additional, Swerdlow, Charles, additional, Tamargo, Juan, additional, Tandri, Harikrishna, additional, Tawil, Rabi, additional, Tedrow, Usha, additional, Terrenoire, Cecile, additional, Tobón, Catalina, additional, Towbin, Jeffrey A., additional, Trayanova, Natalia A., additional, Tristani-Firouzi, Martin, additional, Trohman, Richard G., additional, Tseng, Zian H., additional, Turakhia, Mintu P., additional, Vaidyanathan, Ravi, additional, Valdivia, Héctor H., additional, Valiunas, Virginijus, additional, van der Heyden, Marcel A.G., additional, van der Werf, Christian, additional, Van, George F., additional, Vaseghi, Marmar, additional, Veltmann, Christian, additional, Vetter, Victoria L., additional, Viskin, Sami, additional, Voigt, Niels, additional, Vos, Marc A., additional, Wagner, Galen S., additional, Wang, Paul J., additional, Weerasooriya, Rukshen, additional, Wilde, Arthur A.M., additional, Wilkoff, Bruce L., additional, Wissner, Erik, additional, Woo, Y. Joseph, additional, Yamazaki, Masatoshi, additional, Yang, Felix, additional, Yaniv, Yael, additional, Yap, Sing-Chien, additional, Yee, Raymond, additional, Zarzoso, Manuel, additional, Zeppenfeld, Katja, additional, and Zipes, Douglas P., additional
- Published
- 2014
- Full Text
- View/download PDF
6. Biological Pacing
- Author
-
Rosen, Michael R., primary, Brink, Peter R., additional, Cohen, Ira S., additional, and Robinson, Richard B., additional
- Published
- 2014
- Full Text
- View/download PDF
7. Michael R. Rosen, MD (1938-2023).
- Author
-
Cohen IS, Robinson RB, and Steinberg SF
- Published
- 2023
- Full Text
- View/download PDF
8. Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles.
- Author
-
Esposito C, Machado P, McDonald ME, Savage MP, Fischman D, Mehrotra P, Cohen IS, Ruggiero N 2nd, Walinsky P, Vishnevsky A, Dickie K, Davis M, Forsberg F, and Dave JK
- Subjects
- Humans, Ultrasonography methods, Predictive Value of Tests, Cardiac Catheterization adverse effects, Microbubbles, Contrast Media
- Abstract
Background: Noninvasive and accurate assessment of intracardiac pressures has remained an elusive goal of noninvasive cardiac imaging., Objectives: The purpose of this study was to investigate if errors in intracardiac pressures obtained noninvasively using contrast microbubbles and the subharmonic-aided pressure estimation (SHAPE) technique are <5 mm Hg., Methods: In a nonrandomized institutional review board-approved clinical trial (NCT03243942), patients scheduled for a left-sided and/or right-sided heart catheterization procedure and providing written informed consent were included. A standard-of-care catheterization procedure was performed advancing clinically used pressure catheters into the left and/or right ventricles and/or the aorta. After pressure catheter placement, patients received an infusion of Definity microbubbles (n = 56; 2 vials diluted in 50 mL of saline; infusion rate: 4-10 mL/min) (Lantheus Medical Imaging). Then SHAPE data was acquired using a validated interface developed on a SonixTablet scanner (BK Medical Systems) synchronously with the pressure catheter data. A conversion factor (mm Hg/dB) was derived from SHAPE data and measurements with a SphygmoCor XCEL PWA device (ATCOR Medical) and was combined with SHAPE data from the left and/or the right ventricles to obtain clinically relevant systolic and diastolic ventricular pressures., Results: The mean value of absolute errors for left ventricular minimum and end diastolic pressures were 2.9 ± 2.0 and 1.7 ± 1.2 mm Hg (n = 26), respectively, and for right ventricular systolic pressures was 2.2 ± 1.5 mm Hg (n = 11). Two adverse events occurred during Definity infusion; both were resolved., Conclusions: These results indicate that the SHAPE technique with Definity microbubbles is encouragingly efficacious for obtaining intracardiac pressures noninvasively and accurately. (Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement; NCT03243942)., Competing Interests: Financial Support and Author Disclosures This work was supported in part by the American Heart Association (grant number: 15SDG25740015) and the National Institutes of Health (grant number: R21 HL 130899). Drs Dave, Forsberg, Mehrotra, and Cohen received research support (contrast agent supply) from Lantheus Medical Imaging, and equipment support from ATCOR Medical Inc. Mr Dickie is an employee of Clarius Mobile Health (but did not have direct access to the research data)., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
9. Intercellular delivery of therapeutic oligonucleotides.
- Author
-
Valiunas V, Gordon C, Valiuniene L, Devine D, Lin RZ, Cohen IS, and Brink PR
- Abstract
One promising approach to cancer therapeutics is to induce changes in gene expression that either reduce cancer cell proliferation or induce cancer cell death. Therefore, delivering oligonucleotides (siRNA/miRNA) that target specific genes or gene programs might have a potential therapeutic benefit. The aim of this study was to examine the potential of cell-based delivery of oligonucleotides to cancer cells via two naturally occurring intercellular pathways: gap junctions and vesicular/exosomal traffic. We utilized human mesenchymal stem cells (hMSCs) as delivery cells and chose to deliver in vitro two synthetic oligonucleotides, AllStars HS Cell Death siRNA and miR-16 mimic, as toxic (therapeutic) oligonucleotides targeting three cancer cell lines: prostate (PC3), pancreatic (PANC1) and cervical (HeLa). Both oligonucleotides dramatically reduced cell proliferation and/or induced cell death when transfected directly into target cells and delivery hMSCs. The delivery and target cells we chose express gap junction connexin 43 (Cx43) endogenously (PC3, PANC1, hMSC) or via stable transfection (HeLaCx43). Co-culture of hMSCs (transfected with either toxic oligonucleotide) with any of Cx43 expressing cancer cells induced target cell death (~20% surviving) or senescence (~85% proliferation reduction) over 96 hours. We eliminated gap junction-mediated delivery by using connexin deficient HeLaWT cells or knocking out endogenous Cx43 in PANC1 and PC3 cells via CRISPR/Cas9. Subsequently, all Cx43 deficient target cells co-cultured with the same toxic oligonucleotide loaded hMSCs proliferated, albeit at significantly slower rates, with cell number increasing on average ~2.2-fold (30% of control cells) over 96 hours. Our results show that both gap junction and vesicular/exosomal intercellular delivery pathways from hMSCs to target cancer cells deliver oligonucleotides and function to either induce cell death or significantly reduce their proliferation. Thus, hMSC-based cellular delivery is an effective method of delivering synthetic oligonucleotides that can significantly reduce tumor cell growth and should be further investigated as a possible approach to cancer therapy., Competing Interests: DECLARATION OF INTERESTS The authors declare that they have no conflicts of interest.
- Published
- 2022
- Full Text
- View/download PDF
10. Defining the factors that affect solute permeation of gap junction channels.
- Author
-
Valiunas V, Cohen IS, and Brink PR
- Subjects
- Animals, Humans, Ion Transport physiology, Cell Membrane Permeability physiology, Connexins metabolism, Gap Junctions metabolism, Ion Channels metabolism
- Abstract
This review focuses on the biophysical properties and structure of the pore and vestibule of homotypic gap junction channels as they relate to channel permeability and selectivity. Gap junction channels are unique in their sole role to connect the cytoplasm of two adjacent cells. In general, these channels are considered to be poorly selective, possess open probabilities approximating unity, and exhibit mean open times ranging from milliseconds to seconds. These properties suggest that such channels can function as delivery pathways from cell to cell for solutes that are significantly larger than monovalent ions. We have taken quantitative data from published works concerning unitary conductance, ion flux, and permeability for homotypic connexin 43 (Cx43), Cx40, Cx26, Cx50, and Cx37, and performed a comparative analysis of conductance and/or ion/solute flux versus diffusion coefficient. The analysis of monovalent cation flux portrays the pore as equivalent to an aqueous space where hydrogen bonding and weak interactions with binding sites dominate. For larger solutes, size, shape and charge are also significant components in determining the permeation rate. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
11. Stem cell-based biological pacemakers from proof of principle to therapy: a review.
- Author
-
Chauveau S, Brink PR, and Cohen IS
- Subjects
- Adenoviridae genetics, Arrhythmias, Cardiac pathology, Gene Transfer Techniques, Humans, Mesenchymal Stem Cells cytology, Stem Cells cytology, Arrhythmias, Cardiac therapy, Biological Clocks, Cell- and Tissue-Based Therapy, Genetic Therapy
- Abstract
Electronic pacemakers are the standard therapy for bradycardia-related symptoms but have shortcomings. Over the past 15 years, experimental evidence has demonstrated that gene and cell-based therapies can create a biological pacemaker. Recently, physiologically acceptable rates have been reported with an adenovirus-based approach. However, adenovirus-based protein expression does not last more than 4 weeks, which limits its clinical applicability. Cell-based platforms are potential candidates for longer expression. Currently there are two cell-based approaches being tested: (i) mesenchymal stem cells used as a suitcase for delivering pacemaker genes and (ii) pluripotent stem cells differentiated down a cardiac lineage with endogenous pacemaker activity. This review examines the current achievements in engineering a biological pacemaker, defines the patient population for whom this device would be useful and identifies the challenges still ahead before cell therapy can replace current electronic devices., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
12. Microtubules and angiotensin II receptors contribute to modulation of repolarization induced by ventricular pacing.
- Author
-
Özgen N, Lu Z, Boink GJ, Lau DH, Shlapakova IN, Bobkov Y, Danilo P Jr, Cohen IS, and Rosen MR
- Subjects
- Adaptation, Physiological physiology, Analysis of Variance, Animals, Biopsy, Blotting, Western, Colchicine pharmacology, Dogs, Heart Conduction System drug effects, Kv Channel-Interacting Proteins metabolism, Male, Patch-Clamp Techniques, Potassium Channels drug effects, Cardiac Pacing, Artificial, Heart Conduction System physiology, Losartan pharmacology, Microtubules metabolism, Potassium Channels physiology, Receptors, Angiotensin metabolism
- Abstract
Background: Left ventricular pacing (LVP) in canine heart alters ventricular activation, leading to reduced transient outward potassium current (I(to)), loss of the epicardial action potential notch, and T-wave vector displacement. These repolarization changes, referred to as cardiac memory, are initiated by locally increased angiotensin II (AngII) levels. In HEK293 cells in which Kv4.3 and KChIP2, the channel subunits contributing to I(to), are overexpressed with the AngII receptor 1 (AT1R), AngII induces a decrease in I(to) as the result of internalization of a Kv4.3/KChIP2/AT1R macromolecular complex., Objective: To test the hypothesis that in canine heart in situ, 2h LVP-induced decreases in membrane KChIP2, AT1R, and I(to) are prevented by blocking subunit trafficking., Methods: We used standard electrophysiological, biophysical, and biochemical methods to study 4 groups of dogs: (1) Sham, (2) 2h LVP, (3) LVP + colchicine (microtubule-disrupting agent), and (4) LVP + losartan (AT1R blocker)., Results: The T-wave vector displacement was significantly greater in LVP than in Sham and was inhibited by colchicine or losartan. Epicardial biopsies showed significant decreases in KChIP2 and AT1R proteins in the membrane fraction after LVP but not after sham treatment, and these decreases were prevented by colchicine or losartan. Colchicine but not losartan significantly reduced microtubular polymerization. In isolated ventricular myocytes, AngII-induced I(to) reduction and loss of action potential notch were blocked by colchicine., Conclusions: LVP-induced reduction of KChIP2 in plasma light membranes depends on an AngII-mediated pathway and intact microtubular status. Loss of I(to) and the action potential notch appear to derive from AngII-initiated trafficking of channel subunits., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
13. Biological pacemakers in canines exhibit positive chronotropic response to emotional arousal.
- Author
-
Shlapakova IN, Nearing BD, Lau DH, Boink GJ, Danilo P Jr, Kryukova Y, Robinson RB, Cohen IS, Rosen MR, and Verrier RL
- Subjects
- Adenoviridae genetics, Animals, Atrioventricular Block physiopathology, Atrioventricular Block therapy, Dogs, Electrocardiography, Genetic Therapy, Green Fluorescent Proteins, Heart Rate physiology, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Ion Channels physiology, Luminescent Agents, Pacemaker, Artificial, Arousal physiology, Biological Clocks physiology, Emotions physiology
- Abstract
Background: Biological pacemakers based on the HCN2 channel isoform respond to beta-adrenergic and muscarinic stimulation, suggesting a capacity to respond to autonomic input., Objective: The purpose of this study was to investigate autonomic response to emotional arousal in canines implanted with murine HCN2-based biological pacemakers using gene therapy., Methods: An electronic pacemaker was implanted with its lead in the right ventricular apical endocardium (VVI 35 bpm). An adenoviral HCN2/GFP construct (Ad-HCN2, n = 7) or saline (control, n = 5) was injected into the left bundle branch on day 2 after radiofrequency ablation of the atrioventricular node to induce complete atrioventricular block. Emotional arousal was achieved by presenting food following an overnight fast. Autonomic control was evaluated with Poincaré plots of R-R(N) against R-R(N+1) intervals to characterize heart rate variability (HRV) and with continuous RR interval assessment via 24-hour ambulatory ECG. The 24-hour ECG and Poincaré plot shape were analyzed., Results: During day 1 after biological pacemaker implantation, Poincaré HRV parameters and RR intervals were unchanged with food presentation. However, on day 7, food presentation was accompanied by an increase in HRV (SD1, p < 0.07, and SD2, p < 0.05) and shortening of RR interval (P < .05) in dogs with Ad-HCN2 but not in controls., Conclusion: This is the first demonstration that biological pacemakers are capable of responding to natural arousal stimuli to elicit appropriate chronotropic responses, a potential advantage over electronic pacemakers., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
14. Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction.
- Author
-
Coronel R, Lau DH, Sosunov EA, Janse MJ, Danilo P Jr, Anyukhovsky EP, Wilms-Schopman FJ, Opthof T, Shlapakova IN, Ozgen N, Prestia K, Kryukova Y, Cohen IS, Robinson RB, and Rosen MR
- Subjects
- Action Potentials, Animals, Disease Models, Animal, Dogs, Heart Conduction System physiopathology, Muscle, Skeletal physiology, Myocardial Infarction physiopathology, Sodium Channels biosynthesis
- Abstract
Background: Skeletal muscle sodium channel (Nav1.4) expression in border zone myocardium increases action potential upstroke velocity in depolarized isolated tissue. Because resting membrane potential in the 1-week canine infarct is reduced, we hypothesized that conduction velocity (CV) is greater in Nav1.4 dogs compared with in control dogs., Objective: The purpose of this study was to measure CV in the infarct border zone border in dogs with and without Nav1.4 expression., Methods: Adenovirus was injected in the infarct border zone in 34 dogs. The adenovirus incorporated the Nav1.4- and a green fluorescent protein (GFP) gene (Nav1.4 group, n = 16) or only GFP (n = 18). After 1 week, upstroke velocity and CV were measured by sequential microelectrode recordings at 4 and 7 mM [K(+)] in superfused epicardial slabs. High-density in vivo epicardial activation mapping was performed in a subgroup (8 Nav1.4, 6 GFP) at three to four locations in the border zone. Microscopy and antibody staining confirmed GFP or Nav1.4 expression., Results: Infarct sizes were similar between groups (30.6% +/- 3% of left ventricle mass, mean +/- standard error of the mean). Longitudinal CV was greater in Nav1.4 than in GFP sites (58.5 +/- 1.8 vs. 53.3 +/- 1.2 cm/s, 20 and 15 sites, respectively; P <.05). Transverse CV was not different between the groups. In tissue slabs, dV/dt(max) was higher and CV was greater in Nav1.4 than in control at 7 mM [K(+)] (P <.05). Immunohistochemical Nav1.4 staining was seen at the longitudinal ends of the myocytes., Conclusion: Nav1.4 channels in myocardium surviving 1 week infarction increases longitudinal but not transverse CV, consistent with the increased dV/dt(max) and with the cellular localization of Nav1.4., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
15. HCN212-channel biological pacemakers manifesting ventricular tachyarrhythmias are responsive to treatment with I(f) blockade.
- Author
-
Plotnikov AN, Bucchi A, Shlapakova I, Danilo P Jr, Brink PR, Robinson RB, Cohen IS, and Rosen MR
- Subjects
- Animals, Catheter Ablation, Dogs, Electrophysiology, Ivabradine, Male, Muscle Cells, Rats, Risk Factors, Tachycardia, Ventricular drug therapy, Benzazepines pharmacology, Calcium Channels, Cardiac Pacing, Artificial, Cardiovascular Agents pharmacology, Defibrillators, Implantable, Tachycardia, Ventricular physiopathology, Tachycardia, Ventricular therapy
- Abstract
Background: A potential concern about biological pacemakers is their possible malfunction, which might create ventricular tachycardias (VTs)., Objective: The purpose of this study was to test our hypothesis that should VTs complicate implantation of HCN-channel-based biological pacemakers, they would be suppressed by inhibitors of the pacemaker current, I(f)., Methods: We created a chimeric channel (HCN212) containing the N- and C-termini of mouse HCN2 and the transmembrane region of mouse HCN1 and implanted it in HEK293 cells. Forty-eight hours later, in whole-cell patch clamp recordings, mean steady state block induced by 3 microM ivabradine (IVB) showed HCN1 = HCN212 > HCN2 currents. The HCN212 adenoviral construct was then implanted into the canine left bundle branch in 11 dogs. Complete AV block was created via radiofrequency ablation, and a ventricular demand electronic pacemaker was implanted (VVI 45 bpm). Electrocardiogram, 24-hour Holter monitoring, and pacemaker log record check were performed for 11 days., Results: All dogs developed rapid VT (>120 bpm, maximum rate = 285 +/- 37 bpm) at 0.9 +/- 0.3 days after implantation that persisted through 5 +/- 1 days. IVB, 1 mg/kg over 5 minutes, was administered during rapid VT, and three dogs received a second dose 24 hours later. While VT terminated with IBV in all instances within 3.4 +/- 0.6 minutes, no effect of IVB on sinus rate was noted., Conclusion: We conclude that (1) I(f)-associated tachyarrhythmias-if they occur with HCN-based biological pacemakers-can be controlled with I(f)-inhibiting drugs such as IVB; (2) in vitro, IVB appears to have a greater steady state inhibiting effect on HCN1 and HCN212 isoforms than on HCN4; and (3) VT originating from the HCN212 injection site is suppressed more readily than sinus rhythm. This suggests a selectivity of IVB at the concentration attained for ectopic over HCN4-based pacemaker function. This might confer a therapeutic benefit.
- Published
- 2008
- Full Text
- View/download PDF
16. Two-pore K+ channels, NO and metabolic inhibition.
- Author
-
Lu Z, Gao J, Zuckerman J, Mathias RT, Gaudette G, Krukenkamp I, and Cohen IS
- Subjects
- Animals, Cell Hypoxia, Cells, Cultured, Energy Metabolism drug effects, Guinea Pigs, Ion Channel Gating drug effects, Membrane Potentials drug effects, Metabolic Clearance Rate drug effects, Myocytes, Cardiac drug effects, Porosity, Potassium Channel Blockers administration & dosage, Potassium Channels drug effects, Ion Channel Gating physiology, Membrane Potentials physiology, Myocytes, Cardiac metabolism, Nitric Oxide metabolism, Potassium Channels physiology, Sodium Cyanide administration & dosage
- Abstract
Ischemic preconditioning is a potent endogenous mechanism protecting many organs from the devastating effects of prolonged ischemia. In the heart, NO is one mediator of this myoprotective response thought to involve activation of the K(ATP) channel. Ischemic preconditioning is known to be induced by metabolic inhibition using sodium cyanide (NaCN) in single cardiomyocytes. In the present study, we show for the first time that the end effector channel activated by NaCN has been incorrectly identified. The channel activated is not K(ATP) but instead belongs to the relatively new family of two-pore domain potassium channels (K2P). Further when activated by metabolic ischemia, the amplitude of K2P current is directly modulated by activators and inhibitors of the NO pathway.
- Published
- 2007
- Full Text
- View/download PDF
17. I(f) and the biological pacemaker.
- Author
-
Robinson RB, Brink PR, Cohen IS, and Rosen MR
- Subjects
- Animals, Autonomic Nervous System, Cell Transplantation, Genetic Therapy, Heart Diseases genetics, Heart Diseases physiopathology, Humans, Ion Channels genetics, Protein Isoforms genetics, Protein Isoforms physiology, Sinoatrial Node cytology, Sinoatrial Node innervation, Sinoatrial Node physiology, Heart physiology, Heart Diseases therapy, Heart Rate, Ion Channels physiology
- Abstract
A biological pacemaker based on the HCN gene family, the molecular correlate of the native cardiac pacemaker current, holds promise of enhancing or supplanting current electronic pacemakers by providing autonomic responsiveness of cardiac rate. Gene-based and cell-based delivery of the HCN gene have been employed to produce biological pacemakers. This article reviews efforts to date to create gene- and cell-based biological pacemakers, using both the HCN gene family and other approaches, and discusses what is known about the autonomic responsiveness in each case. Possible future refinements to an HCN based biological pacemaker also are discussed.
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.