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Red Cell Biology & its Disorders
Mental stress causes vasoconstriction in subjects with sickle cell disease and in normal controls
Ferrata Storti Foundation
Haematologica 2020 Volume 105(1):83-90
Payal Shah,1 Maha Khaleel,1 Wanwara Thuptimdang,2 John Sunwoo,2 Saranya Veluswamy,1 Patjanaporn Chalacheva,2 Roberta M. Kato,3 Jon Detterich,4 John C. Wood,2,4 Lonnie Zeltzer,5 Richard Sposto,6 Michael C.K. Khoo2 and Thomas D. Coates1
1Division of Hematology, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles; 2Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles; 3Division of Pulmonology, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles; 4Division of Cardiology, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles; 5Pediatric Pain Program, David Geffen School of Medicine at UCLA, University of California, Los Angeles and 6Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
ABSTRACT
Vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD) and occurs when deoxygenated sickled red blood cells occlude the microvasculature. Any stimulus, such as mental stress, which decreases microvascular blood flow will increase the likelihood of red cell entrapment resulting in local vaso-occlusion and progression to VOC. Neurally mediated vasoconstriction might be the physiological link between crisis triggers and vaso-occlusion. In this study, we determined the effect of mental stress on microvascular blood flow and autonomic nervous system reactivity. Sickle cell patients and controls performed mentally stressful tasks, including a memory task, conflict test and pain anticipation test. Blood flow was measured using photoplethysmography, autonomic reactivity was derived from electrocardiography and perceived stress was measured by the State-Trait Anxiety Inventory questionnaire. Stress tasks induced a significant decrease in microvascular blood flow, parasympathet- ic withdrawal and sympathetic activation in all subjects. Of the various tests, pain anticipation caused the highest degree of vasoconstriction. The magnitude of vasoconstriction, sympathetic activation and perceived stress was greater during the Stroop conflict test than during the N-back memory test, indicating the relationship between magnitude of experimental stress and degree of regional vasoconstriction. Baseline anxiety had a significant effect on the vasoconstrictive response in sickle cell subjects but not in con- trols. In conclusion, mental stress caused vasoconstriction and autonomic nervous system reactivity in all subjects. Although the pattern of responses was not significantly different between the two groups, the consequences of vasoconstriction can be quite significant in SCD because of the resultant entrapment of sickle cells in the microvasculature. This suggests that mental stress can precipitate a VOC in SCD by causing neural-mediated vasocon- striction.
Introduction
Sickle cell disease (SCD) is a genetic disorder in which polymerization of deoxy- genated sickle hemoglobin (HbS) leads to decreased deformability of the normally flexible erythrocytes. These rigid sickle-shaped red blood cells (RBC) can occlude the microvasculature leading to the sudden onset of painful vaso-occlusive episodes (VOC).1,2 After HbS deoxygenates in the capillaries, it takes some time (seconds) for
Correspondence:
THOMAS D. COATES
tcoates@chla.usc.edu
Received: December 6, 2018. Accepted: April 5, 2019. Pre-published: April 11, 2019.
doi:10.3324/haematol.2018.211391
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/1/83
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