The purpose of the Analytical and Phenotyping Core is to provide state-of-the-art cardiovascular and biochemical analysis of sympathetic baroreflex function, including measurements of sympathetic nerve traffic, catechols, and norepinephrine clearance and spillover. This resource has been critical to the recognition and characterization by our group of new disorders involving the autonomic nervous system, such as dopamine-beta-hydroxylase deficiency. A variety of techniques have been established in this Core to support individual projects, including the determination of plasma volume (Project land 4), heart rate and blood pressure variability (Project 1,2,3, and 4), and baroreflex function (Project 1 and 4). Especially Project 2 among all the others will utilize biochemical evaluation of sympathetic activity which complements other methods of autonomic evaluation detailed in the Clinical Core. Expertise in analysis of ultradian rhythms of cardiovascular parameters for phenotyping will be utilized in Project 1, 3, and 4. Project 1 and 4 will use our novel signal processing tools for neurological signals. In addition, we have implemented an animal phenotyping facility, adapting the methods developed to evaluate autonomic function in humans, to the mice which will be used mainly in Project 1. This includes, among other things, monitoring intra-arterial blood pressure in awake unrestricted mice, monitoring renal sympathetic nerve activity, baroreflex testing, osmopressor tests, and high fidelity ECG, in intact and sinoaortic- denervated mice. Genetically-modified mice are increasingly important in translating autonomic knowledge, and this phenotyping mouse laboratory will be essential in this regard. In this funding period, the Core will provide similar biochemical analytical and phenotyping services but with focus on human data including enhanced signal processing, data reduction with automatic database feeds, links between existing databases, development of data exploration tools for all projects.

Public Health Relevance

The Analytical and Phenotyping Core provides methods to determine how well autonomic control is functioning in humans and in mice. It includes analysis of biological samples, assessment of performance of heart and vessels, and central and peripheral autonomic control. Mice with a genetic defect will be used to study a disease of blood pressure control in a way it is not possible to do in humans.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL056693-17
Application #
8458080
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
17
Fiscal Year
2013
Total Cost
$217,887
Indirect Cost
$74,690
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Mar, Philip L; Raj, Satish R (2018) Orthostatic hypotension for the cardiologist. Curr Opin Cardiol 33:66-72
Chaugai, Sandip; Dickson, Alyson L; Shuey, Megan M et al. (2018) Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated Hypotension: A Retrospective Cohort Study. Clin Pharmacol Ther :
van den Berg, Maarten P; Almomani, Rowida; Biaggioni, Italo et al. (2018) Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. Circ Res 122:846-854
Mai, Tu H; Garland, Emily M; Diedrich, André et al. (2017) Hepatic and renal mechanisms underlying the osmopressor response. Auton Neurosci 203:58-66
Kawai, V K; Levinson, R T; Adefurin, A et al. (2017) A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes. Clin Endocrinol (Oxf) 87:149-155
Pezawas, Thomas; Diedrich, André; Robertson, David et al. (2017) Risk of arrhythmic death in ischemic heart disease: a prospective, controlled, observer-blind risk stratification over 10 years. Eur J Clin Invest 47:231-240
Adefurin, A; Ghimire, L V; Kohli, U et al. (2017) Genetic variation in the alpha1B-adrenergic receptor and vascular response. Pharmacogenomics J 17:366-371
Kaufman, Melissa R; Chang-Kit, Laura; Raj, Satish R et al. (2017) Overactive bladder and autonomic dysfunction: Lower urinary tract symptoms in females with postural tachycardia syndrome. Neurourol Urodyn 36:610-613
Shaw, Brett H; Garland, Emily M; Black, Bonnie K et al. (2017) Optimal diagnostic thresholds for diagnosis of orthostatic hypotension with a 'sit-to-stand test'. J Hypertens 35:1019-1025
Kawai, Vivian K; Levinson, Rebecca T; Adefurin, Abiodun et al. (2017) Variation in the ?2A-adrenergic receptor gene and risk of gestational diabetes. Pharmacogenomics 18:1381-1386

Showing the most recent 10 out of 315 publications