Central parasympathetic activation assessed by cardiac vagal motoneuron recordings in rat Emil Toader To cite this version: Emil Toader. Central parasympathetic activation assessed by cardiac vagal motoneuron recordings in rat. Tissues and Organs [q-bio.TO]. Université Claude Bernard - Lyon I, 2008. English. tel-00291046 HAL Id: tel-00291046 https://tel.archives-ouvertes.fr/tel-00291046 Submitted on 26 Jun 2008 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. N° d’ordre : 41-2008 Année 2008 THESE Présentée devant L’UNIVERSITÉ CLAUDE BERNARD – LYON1 pour l’obtention du DIPLOME DE DOCTORAT (arrêté du 7 août 2006) présentée et soutenue publiquement le 28 mars 2008 par Emil-Codrut TOADER ACTIVATION PARASYMPATHIQUE CENTRALE MISE EN EVIDENCE PAR ENREGISTREMENT DES MOTONEURONES CARDIAQUES VAGAUX CHEZ LE RAT CENTRAL PARASYMPATHETIC ACTIVATION ASSESSED BY CARDIAC VAGAL MOTONEURON RECORDINGS IN RAT Directeur de thèse : Luc QUINTIN JURY M. J.M. PEQUIGNOT Président M. R.M. McALLEN Examinateur M. E. MOYSE Rapporteur et Examinateur M. L. QUINTIN Responsable de thèse MME. C. SEVOZ-COUCHE Rapporteur et Examinateur Laboratoire de Physiologie, (CNRS UMR 5123) Directeur: B. ALLARD 2 UNIVERSITE CLAUDE BERNARD - LYON I Président de l’Université M. le Professeur L. COLLET Vice-Président du Conseil Scientifique M. le Professeur J.F. MORNEX Vice-Président du Conseil d’Administration M. le Professeur J. LIETO Vice-Président du Conseil des Etudes et de la Vie Universitaire M. le Professeur D. SIMON Secrétaire Général M. G. GAY SECTEUR SANTE Composantes UFR de Médecine Lyon R.T.H. Laënnec Directeur : M. le Professeur P. COCHAT UFR de Médecine Lyon Grange-Blanche Directeur : M. le Professeur X. MARTIN UFR de Médecine Lyon-Nord Directeur : M. le Professeur J. ETIENNE UFR de Médecine Lyon-Sud Directeur : M. le Professeur F.N. GILLY UFR d’Odontologie Directeur : M. O. ROBIN Institut des Sciences Pharmaceutiques et Biologiques Directeur : M. le Professeur F. LOCHER Institut Techniques de Réadaptation Directeur : M. le Professeur MATILLON Département de Formation et Centre de Recherche en Biologie Directeur : M. le Professeur P. FARGE Humaine SECTEUR SCIENCES Composantes UFR de Physique Directeur : Mme. le Professeur S. FLECK UFR de Biologie Directeur : M. le Professeur H. PINON UFR de Mécanique Directeur : M. le Professeur H. BEN HADID UFR de Génie Electrique et des Procédés Directeur : M. le Professeur G. CLERC UFR Sciences de la Terre Directeur : M. le Professeur P. HANTZPERGUE UFR de Mathématiques Directeur : M. le Professeur M. CHAMARIE UFR d’Informatique Directeur : M. le Professeur S. AKKOUCHE UFR de Chimie Biochimie Directeur : Mme. le Professeur H. PARROT UFR STAPS Directeur : M. C. COLLIGNON Observatoire de Lyon Directeur : M. le Professeur R. BACON Institut des Sciences et des Techniques de l’Ingénieur de Lyon Directeur : M. le Professeur J. LIETO IUT A Directeur : M. le Professeur M. C. COULET IUT B Directeur : M. le Professeur R. LAMARTINE Institut de Science Financière et d'Assurances Directeur : M. le Professeur J.C. AUGROS 3 Acknowledgments This research project would not have been possible without the support of many people, that I would like to acknowledge. First of all I would like to express my gratitude to my supervisor, Dr. Luc QUINTIN for giving me the opportunity to do research projects at the frontier between engineering and medicine. Dr. Quintin was abundantly helpful and always managed for providing the financial means. He also gave me the possibility to acquire important international collaborations. Overall, I think we have demonstrated together that an anesthetist and an electrical engineer can collaborate and obtain good results, despite any difference of any sort between them, in a similar way the sympathetic and parasympathetic systems work together to regulate the blood pressure. I would like to thank Andrei CIVIDJIAN who offered invaluable assistance, support and guidance through my doctorate studies. I am very grateful for his help and uncounted extra-hours spent at the experimental bench with me. I wish him good luck with his ambitious projects. Deepest gratitude is also due to Robin McALLEN without whose knowledge and assistance this study would not have been successful. It was a great personal experience for me to work together with a very experienced researcher who is in the field of extracellular single unit recording of cardiac vagal motoneurones for more than 30 years. Many thanks to Mme Caroline SEVOZ-COUCHE and Emmanuel MOYSE for accepting to assess this PhD thesis and for their constructive suggestions on the manuscript. I am grateful to Mr. PEQUIGNOT Jean-Marc for his continuous support to our team and for his permanent “gentillesse” that he has shown over all these years. The discussions and cooperation with the international partners of our team have contributed substantially to this work. I am, therefore, grateful to: Mrs. Robyn WOODS, who introduced us in the benefic effects of the natriuretic peptides on the heart; Mr. Karel WESSELING, Mr. Berend WESTERHOF and Mr. John KAREMAKER, Amsterdam, who provided deep knowledge in the latest baroreflex assessment method; Mr. Marco diRIENZO and Mr. Paolo CASTIGLIONI, Milano, who offered us expert views in cardiovascular matters. They showed me how important is to share new ideas in the frame of international collaborations in research. 4 Collective thanks to my neighbours in the lab, the « équipe 1 »: Beatrice GEORGES, Colette MOULIN, Marion LE CAVORSIN MOREAU, Frederique COHEN-ADAD, Chantal BONNET, Anne MORALES, Jacques BODENNEC, Amor BELMEGUENAI, Yvette DALMAZ, Silvia ARANEDA, Kunio KITAHAMA, Laurent BEZIN, Aurélien BOUSSOUAR, Rafaat FARES, Pascal SANCHEZ, Jérémie NADAM, Fabrice NAVARRO. I also extend my thanks to the UMR 5123 for providing laboratory facilities. Thanks to Mrs. Marie-Therese BOILLON and Jean-Sebastien GAILLARD for their help in administrative matters. And thanks to Michel ROCHE and Sophie MOHAMED SIDI for their daily care shown to our rodents. I owe thanks to Nicolas RENTERO, whom I never met, but from whom I indirectly inherited a lot of know-how. Thanks to Sebastien CAYZAC who shared with me a brief but collegial period at the bench. Having had a foreigner statute during my doctoral studies, I would also like to convey thanks to the French authorities (and especially to the prefecture of Rhone) for helping with formalities. And of course, as a friend said, for teaching me that patience should not have limits. Special thanks to the CNRS DR7 administrative team of Mme Perichon who demonstrated their ability to specifically supply funds where it is needed. Many thanks to my friends who were always beside me. Special thanks to Liliana for understanding that in-vivo electrophysiological experiments are not compatible with the 35h/week traditional French working schedule. Her great Moldavian cooking saved my life so often late at night and recovered my destroyed moral shape after unsuccessful experiments. Last, but not least, I want to express my love and gratitude to my parents, who continuously supported me in all ways during this adventure I’ve undertaken in research. Thank you all! Funding: Alpha-2 SARL (A. Cividjian, Head); Groupe de Physiologie Appliquée (L. Quintin, Head); CNRS-PICS (2007-2008). 5 Table of contents Acknowledgments ................................................................................................................................... 2 Table of contents ..................................................................................................................................... 5 Glossary of abbreviations........................................................................................................................ 6 Table of figures........................................................................................................................................ 7 INTRODUCTION ..................................................................................................................................... 8 CARDIAC CONTROL BY THE AUTONOMIC NERVOUS SYSTEM.................................................... 12 I. The autonomic nervous system ............................................................................................... 12 II. The baroreflex loop................................................................................................................... 13 III. The von Bezold-Jarisch reflex .................................................................................................. 18 IV. The cardiac vagal motoneurons............................................................................................ 20 IV.1. Location ........................................................................................................................... 20 IV.2. Projections ....................................................................................................................... 22 IV.3. Activity patterns...............................................................................................................