Exercise and Carotid Artery Function in Metabolic Syndrome

The goal of this project is to determine if young MetSyn patients exhibit carotid endothelial dysfunction (ED) in a sex-specific manner and if exercise can acutely restore internal carotid artery (ICA) function.

The investigators will test this by first quantifying ICA endothelial function using an inhaled gas stressor (CO2) to acutely increase ICA shear rate (SR) and measuring the vascular responsiveness to this increased SR. Carotid endothelial function has never been tested in this way in patients with MetSyn before. Then, a 30 min bout of cycling exercise will be performed followed by the same gas stressor test to determine if ICA endothelial function can be acutely improved in MetSyn.

The aims and hypotheses are to:

* Aim 1: Determine if young adults with MetSyn exhibit carotid ED compared to healthy adults. Hypothesis: carotid ED will be present in young adults with MetSyn.
* Aim 2: Determine if sex differences exist in carotid endothelial function in MetSyn. Hypothesis: MetSyn will result in greater declines in carotid endothelial function in females.
* Aim 3: Determine if exercise yields an acute benefit on carotid endothelial function in young adults with MetSyn. Hypothesis: young adults with MetSyn will receive a greater increase in carotid endothelial function from a single bout of exercise than healthy adults.

• exercise (Behavioral): 30 minute bout of cycling
• Diagnostics (Diagnostic test): * Doppler Ultrasound used to non-invasively assess the diameter and blood flow going into an artery, the ICA in this study. * Indirect calorimeter in tandem with semi-recumbent bike used to assess O2 consumption * heart rate monitor
• Inhaled CO2-mixed air (Other): Three gases of different composition are used to ensure that the proper PETCO2 administration desired for this study occurs in tandem with keeping inspired O2 content constant. This is achieved by used a 5% O2, 95% CO2 tank, a 5% O2, 95% N2 tank, and a 100% O2 tank. In tandem, the use of these three tanks allows for precise control of PETCO2 without a change in inspired O2.

Primary outcomes

• Aim 1: Baseline ICA cSMD measures assessed by MetSyn versus healthy controls [baseline]: Internal carotid artery cerebral shear-mediated dilation (cSMD) is measured by doppler ultrasound and reported in percentage increase in diameter. A resting baseline period for 5 minutes breathing room air followed by 30 seconds of breathing CO2-mixed air at +9 mmHg PETCO2 used to evoke an increase in blood flow to the ICA.
• Aim 2: Baseline ICA cSMD measures assessed by MetSyn versus sex [baseline]: Internal carotid artery cerebral shear-mediated dilation is measured by doppler ultrasound and reported in percentage increase in diameter. A resting baseline period for 5 minutes breathing room air followed by 30 seconds of breathing CO2-mixed air at +9 mmHg PETCO2 used to evoke an increase in blood flow to the ICA.
• Aim 3: Post-exercise cSMD response by MetSyn versus healthy controls [measured during exercise and 10 and 60 minutes post-exercise]: Internal carotid artery cerebral shear-mediated dilation is measured by doppler ultrasound and reported in percentage increase in diameter. 30 minutes of exercise on a cycle ergometer will be performed at 80% of the ventilatory threshold determined during the graded exercise test.

Secondary outcomes

• Aim 3: Duration of Response to Exercise [measured during exercise and 10 and 60 minutes post-exercise]: Duration of post-exercise improvements will be investigated by testing ICA cSMD 10 min and 60 min post-exercise. 30 minutes of exercise on a cycle ergometer will be performed at 80% of the ventilatory threshold determined during the graded exercise test. For the duration of the exercise, indirect calorimetry will be used to assess VO2 to confirm the target workload of 80% of the ventilatory threshold. During this 30 minutes of exercise, ICA diameter and velocity will be measured using ultrasonography every 5 minutes for a 2-minute period.

Sex: All, ages: 18 Years to 40 Years, accepts healthy volunteers

Inclusion Criteria (MetSyn cohort):

* Waist circumference greater than 102 cm (males) or 82 cm (females)
* Triglycerides over 150 mg/dL
* HDL cholesterol less than 40 mg/dL (males) or 50 mg/dL (females)
* Blood pressure ≥130/85 mmHg
* Fasting plasma glucose over 110 mg/dL

Inclusion Criteria (Healthy cohort):

\- meet age criteria

Exclusion Criteria:

* Current smoker, defined as more than 5 cigarettes over past 30 days
* Current diagnosis or history of:

  * peripheral vascular disease
  * hepatic disease
  * renal disease
  * lung disease
  * gastrointestinal disorders/bleeding
  * hematologic disease
  * stroke
  * myocardial infarction
  * coronary heart disease
  * congestive heart failure
  * heart surgery
  * sleep apnea
  * autoimmune diseases
  * traumatic brain injury, concussion, stroke, or seizures
  * Asthma
  * Polycystic ovarian syndrome
* Type II diabetes
* Currently pregnant or breastfeeding
* Current musculoskeletal injury Medication use known to influence cardiovascular function, other than oral contraceptives
* Hormonal contraceptive use, such as intrauterine device or hormonal implant use
* Participants with ICAs unsuitable for imaging, as assessed during the screening visit via doppler ultrasonography

Exclusion Criteria (healthy controls only):

* BMI greater than 25 kg/m2
* Blood pressure over 125/80 mmHg
* Meeting any MetSyn criteria listed for MetSyn cohort

• William Schrage, PhD, Principal investigator, University of Wisconsin, Madison