title: Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.
abstract: Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD.
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering University of Southern California, Los Angeles, California, USA chalache@usc.edu.
authors.forename: Patjanaporn
authors.initials: P
authors.lastname: Chalacheva
authors.affiliation: Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA.
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Kato
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering University of Southern California, Los Angeles, California, USA.
authors.forename: Suvimol
authors.initials: S
authors.lastname: Sangkatumvong
authors.affiliation: Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Detterich
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering University of Southern California, Los Angeles, California, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Bush
authors.affiliation: Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.affiliation: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Meiselman
authors.affiliation: Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Coates
authors.affiliation: Department of Biomedical Engineering, Viterbi School of Engineering University of Southern California, Los Angeles, California, USA.
authors.forename: Michael C K
authors.initials: MC
authors.lastname: Khoo
keywords: Autonomic nervous system; cold face stimulation; mathematical model; sickle cell disease