Journal Article

Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease

Khaleel, Maha, Sunwoo, John, Shah, Payal, Coates, Thomas D., Wood, John C., Detterich, Jon A., Zeltzer, Lonnie, Tsao, Jennie, Meiselman, Herbert J., Kato, Roberta M., Khoo, Michael C. K., Chalacheva, Patjanaporn, Thuptimdang, Wanwara, Sposto, Richard

2017

Overview

Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown. In the present study, we employed a mathematical model to decompose the total vasoconstriction response to pain into: 1) the neurogenic component, 2) the vascular response to blood pressure, 3) respiratory coupling and 4) neurogenic-vascular interaction. The model allowed us to quantify the contribution of each component to the total vasoconstriction response. The most salient features of the components were extracted to represent biophysical markers of autonomic and vascular impairment in SCD and controls. These markers provide a means of phenotyping severity of disease in sickle-cell anemia that is based more on underlying physiology than on genotype. The marker of the vascular component (BMv) showed stronger contribution to vasoconstriction in SCD than controls (p = 0.0409), suggesting a dominant myogenic response in the SCD subjects as a consequence of endothelial dysfunction. The marker of neurogenic-vascular interaction (BMn-v) revealed that the interaction reinforced vasoconstriction in SCD but produced vasodilatory response in controls (p = 0.0167). This marked difference in BMn-v suggests that it is the most sensitive marker for quantifying combined alterations in autonomic and vascular function in SCD in response to heat-induced pain.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Anemia / Anemia, Sickle Cell - blood / Anemia, Sickle Cell - physiopathology / Antagonists / Arginine / Arterioles / Autonomic nervous system / Autonomic Nervous System - physiopathology / Baroreceptors / beta-Thalassemia - physiopathology / Bioavailability / Biological markers / Biology and Life Sciences / Biomedical engineering / Biomedical materials / Biophysical Phenomena / Biophysics / Blood / Blood cells / Blood diseases / Blood flow / Blood pressure / Blood Pressure - physiology / Blood vessels / Cancer / Capillaries / Cardiology / Case-Control Studies / Children / Children & youth / Comparative analysis / Complications and side effects / Constrictions / Control / Diseases / Electrophysiology / Engineering / Female / Genetic aspects / Heart rate / Hematology / Hemoglobin / Hospitals / Humans / Hypertension / Kidneys / Male / Markers / Mathematical models / Medicine / Medicine and Health Sciences / Microvessels - physiopathology / Middle Aged / Models, Biological / Mortality / Nervous system / Nitric oxide / Occlusion / Oncology / Pain / Pain - blood / Pain - physiopathology / Pain perception / Pediatrics / Pharmacology / Physical Sciences / Physiological aspects / Polymerization / Rats / Reflexes / Research and Analysis Methods / Respiration / Risk factors / Rodents / Sickle cell anemia / Sickle cell disease / Sickle Cell Trait - physiopathology / Skin / Stimulation / Sympathetic nervous system / Transplantation / Transplants & implants / Vasoconstriction / Vasoconstriction - physiology / VOCs / Volatile organic compounds / Young Adult