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129
5.3.2. Discussion
Decreases in perfusion after sighs were observed in both groups of subjects.
Because not all sighs were associated with peripheral perfusion drops, we speculated that
the mechanism of the sigh-initiated PU drop responses could be nonlinear and involve
thresholding. Nonetheless, co-occurrence of sighs with perfusion drops was statistically
more frequent in the SCD subjects than in the controls. We think that this frequent
reduction in perfusion with sighs in SCD patients, under some conditions, may be
sufficient to initiate vaso-occlusive events.
Peripheral perfusion is controlled by the vascular smooth muscles, which are
innervated by peripheral sympathetic nerves. Neural activity in these nerves has been
shown to be partly influenced by respiration (Eckberg et al., 1985), through multiple
mechanisms. One of which is the hypoxic stress, which have been shown to increase the
sensitivity to hyperventilation- sympathetic nerve response (Somers et al., 1989). It is
widely known that patients with SCD are constantly in some state of hypoxemia
(Hargrave et al., 2003). Consequently, we speculate that these factors may account for the
hypersensitivity of the post-sigh peripheral vasoconstriction reflex in SCD patients.
Analysis of HRV without adjusting for the effect of respiration suggested that
SCD subjects have stronger sympathetic responses and weaker parasympathetic
responses to sighs than the CTL subjects. However, after adjusting for respiration
patterns, the differences in both HFPra and LHRra between the two groups subsided,
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 147 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 129 5.3.2. Discussion Decreases in perfusion after sighs were observed in both groups of subjects. Because not all sighs were associated with peripheral perfusion drops, we speculated that the mechanism of the sigh-initiated PU drop responses could be nonlinear and involve thresholding. Nonetheless, co-occurrence of sighs with perfusion drops was statistically more frequent in the SCD subjects than in the controls. We think that this frequent reduction in perfusion with sighs in SCD patients, under some conditions, may be sufficient to initiate vaso-occlusive events. Peripheral perfusion is controlled by the vascular smooth muscles, which are innervated by peripheral sympathetic nerves. Neural activity in these nerves has been shown to be partly influenced by respiration (Eckberg et al., 1985), through multiple mechanisms. One of which is the hypoxic stress, which have been shown to increase the sensitivity to hyperventilation- sympathetic nerve response (Somers et al., 1989). It is widely known that patients with SCD are constantly in some state of hypoxemia (Hargrave et al., 2003). Consequently, we speculate that these factors may account for the hypersensitivity of the post-sigh peripheral vasoconstriction reflex in SCD patients. Analysis of HRV without adjusting for the effect of respiration suggested that SCD subjects have stronger sympathetic responses and weaker parasympathetic responses to sighs than the CTL subjects. However, after adjusting for respiration patterns, the differences in both HFPra and LHRra between the two groups subsided, |
