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194
These findings of abnormal ANS responses prompted us to further explore their
autonomic response to other external stimuli. We started by measuring the autonomic
response to the cold face test, as it is one of the most widely used tests of the ANS; in
addition, cold weather is also known to trigger VOC. Our results from this test show that
the ANS balance shifted in the CTL subjects to become more parasympathetic dominant
(or less sympathetic) (Section 5.5). This response is to be expected as the cold face test
stimulates the diving reflex, which is known to activate the parasympathetic system.
Nonetheless, we did not observe this response in SCD patients, regardless whether they
had been treated with chronic transfusion or not. This suggests impairment in their
cardiac parasympathetic nervous systems. This result agrees with our results from the
controlled hypoxia and spontaneous sigh experiments.
In addition to assessing the cardiovascular control of SCD subjects using the HRV
analysis, we also applied the minimal model to assess the reflex mechanisms which
control the HRV. We applied this model to assess the source of the abnormality of the
HRV responses to cold face stimulus (Section 5.6). This model showed a tendency for
both ABR and RCC sensitivities to increase during the CFT in the CTLs, but not in the
SCD subjects. We speculate that this absence in ABR and RCC responses in SCD
subjects may be responsible for their absence of the parasympathetic shift in HRV, as
shown in normal controls. However, due to the large inter-subject variability, statistical
significance of these differences was not attained.
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 212 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 194 These findings of abnormal ANS responses prompted us to further explore their autonomic response to other external stimuli. We started by measuring the autonomic response to the cold face test, as it is one of the most widely used tests of the ANS; in addition, cold weather is also known to trigger VOC. Our results from this test show that the ANS balance shifted in the CTL subjects to become more parasympathetic dominant (or less sympathetic) (Section 5.5). This response is to be expected as the cold face test stimulates the diving reflex, which is known to activate the parasympathetic system. Nonetheless, we did not observe this response in SCD patients, regardless whether they had been treated with chronic transfusion or not. This suggests impairment in their cardiac parasympathetic nervous systems. This result agrees with our results from the controlled hypoxia and spontaneous sigh experiments. In addition to assessing the cardiovascular control of SCD subjects using the HRV analysis, we also applied the minimal model to assess the reflex mechanisms which control the HRV. We applied this model to assess the source of the abnormality of the HRV responses to cold face stimulus (Section 5.6). This model showed a tendency for both ABR and RCC sensitivities to increase during the CFT in the CTLs, but not in the SCD subjects. We speculate that this absence in ABR and RCC responses in SCD subjects may be responsible for their absence of the parasympathetic shift in HRV, as shown in normal controls. However, due to the large inter-subject variability, statistical significance of these differences was not attained. |
