Page 197 |
Save page Remove page | Previous | 197 of 226 | Next |
|
small (250x250 max)
medium (500x500 max)
Large (1000x1000 max)
Extra Large
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
|
179
To dissociate the effect of central sympathetic control from the effect of the
endothelial local vasodilator, especially NO, to the vascular tone, we will use FMD to
stimulate the NO production on the brachial artery of one arm and measure the
subsequent peripheral perfusion responses on both arms. Changes in peripheral perfusion
observed by laser Doppler could be due to either the NO or the CNS effect. To be able to
dissociate the two effects, we propose a model which employs continuous measurement
of blood pressure as well as perfusion from 2 locations; ipsi- and contra-lateral to the
cuffed arm in the FMD experiment (experimental details can be found in Chapter 2). On
the contra-lateral limb, change in perfusion is assumed to be a function of peripheral
sympathetic modulation alone as there was minimal (or no) change in the shear rate thus
the change in NO level on this limb can be considered negligible. On the other hand
(literally), when the blood pressure cuff is released from the arm, the change in perfusion
on the ipsi-lateral limb is assumed to be a function of both peripheral sympathetic
modulation and change in NO level due to change in shear rate.
6.2.2. Computational Technique
For each arm, the measured perfusion is assumed to be a summation of the
sympathetic effect and the endothelial effect, while blood pressure is treated as a driving
input (Figure 6.2). On the ipsi-lateral side of the FMD, the effect of endothelial is
strongly presented since the change in shear rate caused by increase in flow from the
release of pressure cuff will cause an increase in NO production, which results in
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 197 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 179 To dissociate the effect of central sympathetic control from the effect of the endothelial local vasodilator, especially NO, to the vascular tone, we will use FMD to stimulate the NO production on the brachial artery of one arm and measure the subsequent peripheral perfusion responses on both arms. Changes in peripheral perfusion observed by laser Doppler could be due to either the NO or the CNS effect. To be able to dissociate the two effects, we propose a model which employs continuous measurement of blood pressure as well as perfusion from 2 locations; ipsi- and contra-lateral to the cuffed arm in the FMD experiment (experimental details can be found in Chapter 2). On the contra-lateral limb, change in perfusion is assumed to be a function of peripheral sympathetic modulation alone as there was minimal (or no) change in the shear rate thus the change in NO level on this limb can be considered negligible. On the other hand (literally), when the blood pressure cuff is released from the arm, the change in perfusion on the ipsi-lateral limb is assumed to be a function of both peripheral sympathetic modulation and change in NO level due to change in shear rate. 6.2.2. Computational Technique For each arm, the measured perfusion is assumed to be a summation of the sympathetic effect and the endothelial effect, while blood pressure is treated as a driving input (Figure 6.2). On the ipsi-lateral side of the FMD, the effect of endothelial is strongly presented since the change in shear rate caused by increase in flow from the release of pressure cuff will cause an increase in NO production, which results in |
