158. Stabilization Of The Cardiac Nervous System

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158. Stabilization Of The Cardiac Nervous System

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Syllabus

ABSTRACT ………………………………………………………………………… 2
DEDICATION …………………………………………………………………….. 4
ACKNOWLEDGEMENTS ………………………………………………………… 5
LIST OF TABLES ………………………………………………………………….. 11
LIST OF FIGURES ………………………………………………………………… 12
LIST OF ABBREVIATIONS ………………………………………………………. 13
Chapter
1. INTRODUCTION ……………………………………………………………….. 15
The Cardiac Nervous System…………………………………………………. 15
Ischemic Cardiac Disease and Its Effect on the Cardiac Nervous System……. 17
Cardiac Arrhythmias and the Cardiac Nervous System………………………. 19
Neuromodulation as a Novel Approach to Treat Heart Disease……………… 20
Specific Aims …………………………………………………………………… 25
2. ACTIVATED CRANIAL CERVICAL CORD NEURONS AFFECT LEFT VENTRICULAR
INFARCT SIZE AND THE POTENTIAL FOR SUDDEN CARDIAC DEATH … 28
Abstract ………………………………………………………………………….. 29
Introduction …………………………………………………………………. 30
Materials and Methods ……………………………………………………….. 32
Subjects ……………………………………………………………… 32
Surgical preparation …………………………………………………. 32
Experimental protocols ………………………………………………. 34
Pre-emptive electrical neuromodulation ………………………………. 35

Infarct measurement ………………………………………………….. 37
Immunohistochemistry ……………………………………………….. 38
Statistical analysis ……………………………………………………… 39
Results ……………………………………………………………………….. 39
Hemodynamic variables ………………………………………………. 39
Effects of C1-C2 SCS on Infarct size ………………………………… 42
Effects of C1-C2 SCS on ventricular arrhythmogenic potential ………. 44
Effects of C1-C2 SCS on thoracic dorsal horn activity ………………. 45
Discussion ……………………………………………………………………. 46
Cervical cord neuromodulation of ischemia-induced myocardial
infarction…………………………………………………………….. 48
Neuromodulation therapy and arrhythmias …………………………. 49
Perspectives and significance………………………………………… 51
Acknowledgements …………………………………………………………….. 52
References ……………………………………………………………………… 53
3. SPINAL CORD STIMULATION MITIGATES CARDIAC PRIMARY AFFERENT
NEURONAL TRANDUCTION OF MYOCARDIAL ISCHEMIA WITHOUT ANTIDROMIC
ACTIVATION ………………………………………………………………………. 59
Abstract ………………………………………………………………………… 60
Introduction …………………………………………………………………. 61
Materials and Methods ………………………………………………………. 62
Animal preparation ………………………………………………….. 62
Spinal cord stimulation (SCS)………………………………………… 63
Afferent neuronal activity recording…………………………………. 64

Protocols employed …………………………………………………. 65
Suprathreshold SCS …………………………………………………. 66
Data analysis …………………………………………………………. 66
Results ………………………………………………………………………. 67
Hemodynamic data ………………………………………………….. 67
Dorsal root ganglion afferent neuronal activity ……………………….. 67
Nodose ganglion afferent neuronal activity ………………………….. 69
DRG activity during supra-threshold SCS ……………………………. 70
Discussion …………………………………………………………………… 71
Perspectives and significance …………………………………………………………. 73
Acknowledgements ………………………………………………………….. 74
References ……………………………………………………………………… 75
4. NEUROMODULATION TARGETS INTRINSIC CARDIAC NEURONS TO ATTENUATE
NEURONALLY-MEDIATED ATRIAL ARRHYTHMIAS ……………………….. 78
Abstract ………………………………………………………………………. 79
Introduction …………………………………………………………………. 80
Materials and Methods ………………………………………………………. 81
Animal Preparation…………………………………………………….. 81
Neural Tracer Injection……………………………………………….. 81
Immunohistochemistry………………………………………………….. 82
Hemodynamic Recording…………………………………………………….. 83
Spinal Cord Stimulation (SCS)………………………………………… 84
Mediastinal Nerve Stimulation – MSNS……………………………… 85
Neuronal Recording…………………………………………………. 85

Treatment Groups…………………………………………………… 86
Data Analysis………………………………………………………… 86
Results………………………………………………………………………… 87
Neuroanatomical Data……………………………………………….. 87
Intrinsic Cardiac Neuronal Activity…………………………………….. 90
MSNS-Induced Bradycardia………………………………………….. 92
Time Controls………………………………………………………… 93
Atrial Rhythms……………………………………………………….. 94
Discussion…………………………………………………………………….. 96
Perspectives and Significance………………………………………………… 98
Acknowledgements …………………………………………………………………. 99
References ……………………………………………………………………… 100
5. SUMMARY ………………………………………………………………………. 105
Organization of the Cardiac Nervous System for Control of Normal
and Stressed Hearts………………………………………………….. 106
Neuromodulation as a Therapeutic Approach for Control of
Cardiac Nervous System and Heart …………………………………… 108
Neuromodulation of the Ischemic Heart ……………………………………. 110
SCS Effects on Afferent Transduction ……………………………….. 110
SCS Effects on Infarct Size …………………………………………. 111
SCS and the Potential for ischemia-induced SCD …………………… 114
Neuromodulation of Arrhythmias …………………………………… 115
Conclusions………………………………………………………………….. 116
Topics for Future Study………………………………………………………. 116

REFERENCES ……………………………………………………………………… 118
VITA ………………………………………………………………………………… 133

……………………………………………………………………………………………………………………………………………………………………………………………………………………

 

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