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Effects of Chemoreceptor and Baroreceptor Inputs on the Termination of Inspiration Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 1980 Effects of Chemoreceptor and Baroreceptor Inputs on the Termination of Inspiration Dexter Franklin Speck Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Physiology Commons Recommended Citation Speck, Dexter Franklin, "Effects of Chemoreceptor and Baroreceptor Inputs on the Termination of Inspiration" (1980). Dissertations. 1853. https://ecommons.luc.edu/luc_diss/1853 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 1980 Dexter Franklin Speck EFFECTS OF CHEMORECEPTOR AND BARORECEPTOR INPUTS ON THE TERMINATION OF INSPIRATION by Dexter Franklin Speck A Dissertation Submitted to the Faculty of the Graduate School of Loyola University of Chicago in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 1980 ACKNOWLEDGEMENTS The author gratefully acknowledges the assistance rendered by all members of the committee. A special thank you goes to Dr. \.Jebber for his guidance and patience throughout t~e writing of this disser­ tation. iii BIOGRAPHY Dexter F. Speck is the son of Bursie v. Speck and Myrna Y. Speck. He was born June 4, 1955 in Altoona, Pennsylvania. He attended elemen­ tary school and high school in the Huntingdon Area public school system. In September, 1973, Dexter entered Wheaton College in Wheaton, Illinois. He graduated ctnn laude from Wheaton College with a Bachelor of Science degree in Biology. The author began his graduate studies in July of 1976 in the Department of Physiology, Loyola University Medical Center. During the past three years, he has worked under the direction of Dr. Charles L. Webber, Jr. On March 1, 1980, Dexter married Pamela Jo Pickens of Moberly, Missouri. Pamela is currently employed at Central DuPage Hospital as a surgical technologist. In July, the author will begin two years of postdoctoral study at Northwestern University Medical Center in Chicago v*1ere he will be studying under the direction of Dr. Jack L. Feldman. iv PUBLICATIONS PAPERS 1. Bruce, D.S., D.F. SPECK, T.A. Magary and J.S. I.J"esterhoven. A comparative study of diving physiology. The Physiology Teacher 4(4): 8-10, 1975. 2. SPECK, D.F. and D.S. Bruce. Effects of varying thermal and apneic conditions on the human diving reflex. Undersea Bio­ medical Journal 5(1): 9-14, 1978. 3. Bruce, D.S. and D.F. SPECK. Human simulated diving experiments. The Physiologist 22(5): 39-40, 1979. 4. SPECK, D.F. and C.L. I.J"ebber, Jr. Thoracic dorsal rhizotomy in the anesthetized cat: maintenance of eupnic breathing: Respir. Physiol. 38: 347-357, 1979. 5. SPECK, D.F. and C.L. Webber, Jr. Time course of intercostal afferent termination of the inspiratory process. Respir. Physiol.: Submitted, 1980. ABSTRACTS 1. SPECK, D.F. and C.L. Webber, Jr. Effect of thoracic dorsal rhizotomy on respiratory parameters in quiet breathing. Fed. Proc. 38: 368, 1978. 2. SPECK, D.F. and C.L. Webber, Jr. Time-course of inspiratory off- switch activation by intercostal afferent stimulation. Fed. Proc. 38: 1229, 1979. 3. SPECK, D.F. and C.L. Webber, Jr. Effects of cerebellectomy and C0 on the intercostal nerve activation of the inspiratory 2 off-switch. The Physiologist 22(4): 118, 1979. 4. Hebber, C.L., Jr., and D.F. SPECK. An experimental model of biot periodic breathing in the cat. The Physiologist 22(4): 130, 1979. S. Webber, C.L., Jr., and D.F. SPECK. Control of expiratory timing in biot periodic breathing cats. Fed. Proc. 39: 952, 1980. 6. SPECK, D.F. and C.L. I.Jebber, Jr. Effects of oxygen on the inter- costal nerve activation of inspiratory termination. Clinical Research: In press, 1980. v TABLE OF CONTENTS Chapter Page ACKNOWLEDGEMENTS • •••••••••••••••••••••••••••••••••••••••••••••••••••• iii BIOGRAPHY • •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• i v PUBLICATIONS • •••••••••••••••••••••••••••••••••••••••••••••••••••••••••• v TABLE OF CONTENTS ••••••••••••••••••••••••••••••••••••••••••••••••••••• vi LIST OF TABLES••••••••••••••••••••••••••••••••••••••••••••••••••••••viii LIST OF ILLUSTRATIONS•••••••••••••••••••••••••••••••••••••••••••••••••ix I. INTRODUCTION. ••• •••• ••••••• ••• •••••••••••• •• •• ••••• •• •• ••• •• .1 I I • LITERATURE REV! EW • ••••••••••••••••••••••••••••••••••••••••••• 2 A. Inspiratory Off-Switch MeChanism •••••••••••••••••••••••• 2 1. Conceptual development•••••••••••••••••••••••••••••2 2. Excitatory inputs••••••••••••••••••••••••••••••••••S 3. Localization••••••••••••••••••••••••••••••••••••••14 B. Intercostal Respiratory Afferents, ••••••••••••••••••••• 16 c. Chemoreceptor Modulation of ~espiration .•.••••••••••••• 22 1. Response to Hypoxia ••••••••••••••••••••••••••••••• 23 2. Respiratory Modulation by Carbon Dioxide, ••••••••• 27 D. Baroreceptor Modulation of Respiration ••••••••••••••••• 31 III. METHODS • •••••••••••••••••••••••••••••• , • , • , • , ••••••••••••••• 36 A. Surgical Preparation•••••••••••••••••••••••••••••••••••36 B. Experimental Design and Statistics ••••••••••••••••••••• 45 C. Experimental Groups••••••••••••••••••••••••••••••••••••47 IV. RESULTS. ••••••••••••••••••••••••••••••••••••••••••••••••••••54 v. DISCUSSION••••••••••••••••••••••••••••••••••••••••••••••••••83 A. Off-Switch Activation by Intercostal Nerve Stimulation •••••••••••••••••••••••••••••••••••••• 83 B. Off-Switch Activation by Somatic (~e rve Stimulation ••••••••••••• , ••••• , ••••• , •••••••••••• 8 3 C. Chemoreceptor Modulation of Off-Switching Excitability ••••••••••.• , ••••• .•.•.•.•.•.• ••• •.••.••••• 89 1. Response to carbon dioxide ••••••••••••••••••••••••• 91 2, Response to oxygen •••••.•.•.•••.•.•••.•••••••••• , •• q4 vi Chapter Page D. Baroreceptor Modulation of Off-Switch Excitability •••••• 97 VI. CONCLUSIONS ••••••••••••••••••••••••••••••••••••••••••••••••• 102 VI I. BIBLIOGRAPHY •••••••••••••••••••••••••••••••••••••••••••••••• 1 04 APPENDIX A ••••••• •• ••••••• ••• ••••••••••••••••••• •• •• ••••••••••••••• ••• 120 APPENDIX B •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 125 vii LIST OF TABLES Table Page 1. Respiratory Response to Somatic Nerve Stimulation ••••••••••••• S8 2. Respiratory Responses to the Eight Experimental Phases of Group VI I ••••••••••••••••• , ••••• , • , ••• , • , • , ••••••••• 7 2 viii LIST OF ILLUSTRATIONS Figure Page 1. Instrumentation of Experimental Preparation •••••••••••••••••• 42 2. Example of Oscilloscope Tracing •••••••••••••••••••••••••••••• 43 3. Example of Polygraph Record••••••••••••••••••••••••••••••••••44 4. Isolated Carotid Sinus Preparation, •••••••••••••••••••••••••• 52 5. Individual Responses to Left T6 Intercostal Nerve Stim.ulation • •• ••• •••••••••••.•.•••.•.•.•••••••••••••••• 56 6. Time-course of Off-switch Excitability Assessed by Intercostal Nerve Stimulation, •••••••••••••••••••••••••••• 57 7. Response to Different Carbon Dioxide Levels •••••••••••••••••• 60 8. Response to Cerebellectomy ••••••••••••••••••••••••••••••••••• 63 9. Response to Different Carbon Dioxide Levels with Intact Cerebellum •••••••••••••••••••••••••••••••• 64 10. Response to Different Carbon Dioxide Levels after Cerebellectomy •••••••••••••••••••••••••••••••••• 65 11. Response to Different Oxygen Concetrations ••••••••••••••••••• 67 12. Cardiovascular and Respiratory Responses-· during Experiments o£ Group VII., •••••••••••••••••••••••••••• 69 13. Cardiovascular and Respiratory Responses to Bilateral Carotid Occlusion ••••••••••••••••••••••••••••••• 71 14. Response to Normoxic Hypercapnia and Isocapnic Hyperoxia••••••••••••••••••••••••••••••••••••••74 15. Response to Carotid Sinus Nerve Section •••••••••••••••••••••• 75 16. Response to Normoxic Hypercapnia and Isocapnic Hyperoxia after Crotid Sinus Denervation ••••••••••••••••••••• 76 17. Cardiovascular and Respiratory Responses to Alteration of Carotid Sinus Pressure, •••••••••••••••••••••••• 77 ix Figure Page 18. Alteration of Systemic Arterial Pressure ••••••••••••••••••••• 79 19. Cardiovascular and Respiratory Response to Alteration of Carotid Sinus Pressure ••••••••••••••••••••••••• 80 20. Theoretical Model of Off-switch Function ••••• , ••••••••••••••• 81 21. Theoretical Diagram of Effects of Hypoxia •••••••••••••••••••• 86 22. Theoretical Diagram of Effects of Hypoxia ••••••••••••• , •••••• 93 X CHAPTER I INTRODUCTION The mechanisms that detennine respiratory rhythmicity have fascinated investigators for many years, Although the genesis of this oscillating neural cycle is still not completely understood, sufficient experimental evidence has been acctmlulaterl to pemit the theoretical construction of several different models of respiratory rhythmicity. Most of these models subdivide the respiratory cycle into four specific processes: expiration, the onset of inspiratory activity, the aug­ menting phase of ins pi rat ion and the t emination of inspiratory acti­ vity. These processes act together to determine the duration of both inspiration and expiration. This study was designed to investigate the influences exerted on the inspiratory tenninating process by several known respiratory modu­ lating stimuli. A technique for assessing the inspiratory-to-expiratory switching threshold has been developed and sub sequent ly
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