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10
1.2.2.2. Extrinsic control of peripheral perfusion
In addition to intrinsic regulation of perfusion which originate in the smooth
muscle cells themselves, smooth muscles in blood vessels are also innervated with
sympathetic nerve fibers (Berne, & Levy, 2001). These nerve activities help maintain
tonic level of peripheral resistance. When the nerves are innervated, blood pressure
increases; while when the magnitude or frequency of the nerve firing increases, the blood
pressure decrease (Persson, 1996). The parasympathetic nerves, on the other hand,
innervate relatively few blood vessels and thus have little effect on the peripheral
resistance.
1.3. Sickle Cell Disease and Autonomic Dysfunction
Cardiovascular dysfunctions have also been correlated with ANS abnormalities in
the multiple diseases, including diabetes, sleep apnea, and heart disease. In SCD patients,
some degree of physiological cardiovascular adaptation has been reported, including
elevations in heart rate and declines in cardiac output, resulting primarily from associated
chronic hemolytic anemia (Lester et al., 1990; Batra et al., 2002). Transient cardiac
dysfunction and myocardial ischemia have also been reported during their crises (Norris
et al., 1991; Deymann, & Goertz, 2003). Although acute atherosclerosis-related
myocardial infarctions are rare in SCD patients, diverse cardiovascular anomalies
including heart murmurs, cardiomegaly, biventricular hypertrophy, and abnormalities in
the cardiac conducting system have been described by multiple researchers (Assanasen et
al., 2003; Pavlu et al., 2007; Batra et al., 2002; James et al., 1994; Norris et al., 1991;
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 28 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 10 1.2.2.2. Extrinsic control of peripheral perfusion In addition to intrinsic regulation of perfusion which originate in the smooth muscle cells themselves, smooth muscles in blood vessels are also innervated with sympathetic nerve fibers (Berne, & Levy, 2001). These nerve activities help maintain tonic level of peripheral resistance. When the nerves are innervated, blood pressure increases; while when the magnitude or frequency of the nerve firing increases, the blood pressure decrease (Persson, 1996). The parasympathetic nerves, on the other hand, innervate relatively few blood vessels and thus have little effect on the peripheral resistance. 1.3. Sickle Cell Disease and Autonomic Dysfunction Cardiovascular dysfunctions have also been correlated with ANS abnormalities in the multiple diseases, including diabetes, sleep apnea, and heart disease. In SCD patients, some degree of physiological cardiovascular adaptation has been reported, including elevations in heart rate and declines in cardiac output, resulting primarily from associated chronic hemolytic anemia (Lester et al., 1990; Batra et al., 2002). Transient cardiac dysfunction and myocardial ischemia have also been reported during their crises (Norris et al., 1991; Deymann, & Goertz, 2003). Although acute atherosclerosis-related myocardial infarctions are rare in SCD patients, diverse cardiovascular anomalies including heart murmurs, cardiomegaly, biventricular hypertrophy, and abnormalities in the cardiac conducting system have been described by multiple researchers (Assanasen et al., 2003; Pavlu et al., 2007; Batra et al., 2002; James et al., 1994; Norris et al., 1991; |
