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172
Measures of changes in parasympathetic modulations (HFP, HFPra, and Grsa)
showed positive correlations to parameters related to red blood content (hemoglobin,
hematocrit, RBC count), except reticulocyte count, which is usually high in SCD patients
due to compensation of the bone marrow for their anemia. This suggests that the degree
of anemia (decreased hemoglobin, RBC count, and hematocrit) is associated with the
sensitivity of hypoxia response. This means that, following a hypoxic stimulus, a more
anemic patient will become more tachycardia and had a stronger parasympathetic
withdrawal.
On the other hand, parameters related to white blood content (white blood cell
count, and ANC), inflammation (hs-CRP), and hemoglobin A2 show negative
correlations to HRV parameters related to changes in parasympathetic modulations. In
other words, parameters related to white blood cells were correlated to RRI drops and
parasympathetic withdrawal. Since SCD is known to be an inflammatory disease, i.e.
sickle cell patients are constantly in an inflammation state (Hebbel et al., 2004), this
result suggests that the more inflamed the SCD patient, the more sensitive his/her ANS
response to hypoxia will be.
However, the decrease in RBC and the increase in WBC contents in SCD patients
might be correlated. Therefore, one may have a confounding effect on the others. As a
result, we created a scatter plot between RBC count and WBC count (Figure 5.30) which
shows a significant correlation between RBC count and WBC count (R2 = 0.522, p <
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 190 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 172 Measures of changes in parasympathetic modulations (HFP, HFPra, and Grsa) showed positive correlations to parameters related to red blood content (hemoglobin, hematocrit, RBC count), except reticulocyte count, which is usually high in SCD patients due to compensation of the bone marrow for their anemia. This suggests that the degree of anemia (decreased hemoglobin, RBC count, and hematocrit) is associated with the sensitivity of hypoxia response. This means that, following a hypoxic stimulus, a more anemic patient will become more tachycardia and had a stronger parasympathetic withdrawal. On the other hand, parameters related to white blood content (white blood cell count, and ANC), inflammation (hs-CRP), and hemoglobin A2 show negative correlations to HRV parameters related to changes in parasympathetic modulations. In other words, parameters related to white blood cells were correlated to RRI drops and parasympathetic withdrawal. Since SCD is known to be an inflammatory disease, i.e. sickle cell patients are constantly in an inflammation state (Hebbel et al., 2004), this result suggests that the more inflamed the SCD patient, the more sensitive his/her ANS response to hypoxia will be. However, the decrease in RBC and the increase in WBC contents in SCD patients might be correlated. Therefore, one may have a confounding effect on the others. As a result, we created a scatter plot between RBC count and WBC count (Figure 5.30) which shows a significant correlation between RBC count and WBC count (R2 = 0.522, p < |
