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iii
Acknowledgements
Throughout my years in the PhD program, I owed my gratitude to great many
people. Without whom this dissertation would not have been possible and my graduate
school experience would not have been as memorable.
My deepest gratitude is to my advisor, Dr. Michael C.K. Khoo. His advice has
guided me through my PhD progress. I felt truly fortunate to have a very supportive
advisor that allows me the freedom to explore different ideas while always be there to
guide me to the right path.
I would also like to express my great gratitude to my co-advisor, Dr. Thomas D.
Coates. I have learned so much from your vast knowledge. His passion has inspired me to
continue to do research. I am also very thankful for the tremendous amount of time his
have spent on teaching me not only scientific and medical stuffs, but also hours and hours
that he spent training me to give a talk and revising my writings.
I would like to thank Drs. John Wood, Herbert Meiselman, and David D’Argenio
for your guidance during my qualifying exam and beyond. I am grateful for all valuable
comments and suggestions which Dr. Wood and Dr. Meiselman have shared during our
weekly research group meetings. I am deeply grateful to both for many advices that
helped me both on the technical and medical aspects of my work.
The completion of my research work would not have been possible if not for the
contributions from the entire sickle cell research team at CHLA and USC. Drs. Thomas
Coates (my co-advisor), Roberta Kato, and Jon Detterich have spent numerous times
Object Description
| Title | Modeling of cardiovascular autonomic control in sickle cell disease |
| Author | Sangkatumvong, Suvimol "Ming" |
| Author email | sangkatu@usc.edu; mingsuvimol@hotmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biomedical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2011-03-03 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-04-26 |
| Advisor (committee chair) |
Khoo, Michael C.K. Coates, Thomas |
| Advisor (committee member) |
Wood, John C. Meiselman, Herbert J. |
| Abstract | Sickle cell disease (SCD) is a genetic disorder that is characterized by recurrent episodes of vaso-occlusive crisis (VOC) from the sickling behavior of red blood cells. Currently, no technique can distinguish the cause or predict the occurrence of a crisis accurately and reliably. One area which has rarely been studied in SCD patients is their autonomic nervous system (ANS). Since the ANS is responsible for the moment-to-moment control of the vascular tone, we hypothesized that the ANS plays an important role in the initiation of their VOC. Computational techniques, including spectral analysis of HRV and a model which characterizes the dynamics of baroreflex and respiratory-cardiac coupling, were used to assess cardiovascular autonomic control in SCD patients and normal control (CTL) subjects. These analysis techniques were applied to responses elicited from the subjects during the application of non-invasive and easily reproducible physiological interventions, such as transient-controlled hypoxia and the cold face test.; Our results demonstrate impairment in the ANS in SCD patients. In particular, hypoxic responses in SCD subjects showed a significantly stronger parasympathetic withdrawal compared to the CTLs. Furthermore, the autonomic responses to the cold face stimulus in SCD subjects showed an absence of the shift to parasympathetic dominance, as evidenced in the CTLs. In addition to the HRV analysis, model-based assessment also revealed the absence of both arterial baroreflex and respiratory-cardiac coupling augmentations in SCD patients during the cold face stimulus, while in CTL subjects both mechanisms showed tendencies to increase during the test.; During the data analysis period, we noticed that spontaneous sighs triggered marked periodic drops in peripheral microvascular perfusion. While the sigh frequency was the same in both groups, the probability of a sigh inducing a perfusion drop was significantly higher in SCD subjects in comparison to the CTLs. Evidence for sigh-induced sympathetic nervous system dominance was seen in SCD subjects, but was not significant in CTL. HRV analysis suggested that the cardiac ANS responses to sighs are not different between the two groups, after adjusting for the effect of post-sigh respiration. However, the peripheral sympathetic response in SCD subjects appeared to be enhanced in this group relative to the CTLs; and, furthermore, sighs may play a role in initiation of vaso-occlusive events in this group of patients.; In brief, all assessments we performed in this study suggested that the ANS responses to perturbations in SCD patients are more biased toward parasympathetic withdrawal and sympathetic activation, compared to normal controls. The complete mechanism is still a topic of investigation. Thus far, we have shown a relationship between the degree of this abnormality and the degree of both the anemia and infection/inflammation. We suspect that a mechanism related to the inflammatory reflex might play an important role in the ANS impairment in this group of patients.; In conclusion, this study draws attention to an enhanced ANS-mediated peripheral sympathetic driven vasoconstriction in SCD that could increase red cell retention in the microvasculature, promoting vaso-occlusion. This cascade of events could be the mechanism which triggers the VOC. |
| Keyword | autonomic nervous system; heart rate variability; respiration; sickle cell disease; physiological system modeling; sympathetic; parasympathetic; minimal model; baroreflex; respiratory-cardiac coupling; hypoxia; sigh; cold face test; cardiovascular autonomic control |
| Geographic subject | medical facilities: Childrens' Hospital Los Angeles |
| Geographic subject (city or populated place) | Los Angeles |
| Geographic subject (state) | California |
| Geographic subject (country) | USA |
| Coverage date | 2005/2010 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3781 |
| Contributing entity | University of Southern California |
| Rights | Sangkatumvong, Suvimol "Ming" |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-Sangkatumvong-4436 |
| Archival file | uscthesesreloadpub_Volume23/etd-Sangkatumvong-4436.pdf |
Description
| Title | Page 3 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | iii Acknowledgements Throughout my years in the PhD program, I owed my gratitude to great many people. Without whom this dissertation would not have been possible and my graduate school experience would not have been as memorable. My deepest gratitude is to my advisor, Dr. Michael C.K. Khoo. His advice has guided me through my PhD progress. I felt truly fortunate to have a very supportive advisor that allows me the freedom to explore different ideas while always be there to guide me to the right path. I would also like to express my great gratitude to my co-advisor, Dr. Thomas D. Coates. I have learned so much from your vast knowledge. His passion has inspired me to continue to do research. I am also very thankful for the tremendous amount of time his have spent on teaching me not only scientific and medical stuffs, but also hours and hours that he spent training me to give a talk and revising my writings. I would like to thank Drs. John Wood, Herbert Meiselman, and David D’Argenio for your guidance during my qualifying exam and beyond. I am grateful for all valuable comments and suggestions which Dr. Wood and Dr. Meiselman have shared during our weekly research group meetings. I am deeply grateful to both for many advices that helped me both on the technical and medical aspects of my work. The completion of my research work would not have been possible if not for the contributions from the entire sickle cell research team at CHLA and USC. Drs. Thomas Coates (my co-advisor), Roberta Kato, and Jon Detterich have spent numerous times |
