Dose Response of Epinephrine

Hypoglycemia Associated Autonomic Dysfunction Dose Response of Epinephrine

Epinephrine is the principal physiologic defense against hypoglycemia in type 1 and longer duration type 2 DM. Despite this, it is unknown how epinephrine regulates in-vivo endothelial function and atherothrombotic balance in humans. The specific aim of our study will be to determine the dose response effects of the key ANS counterregulatory hormone epinephrine on endothelial function, fibrinolytic balance and pro-atherogenic inflammatory mechanisms in healthy humans.

Inclusion Criteria:

• healthy controls age 18-55 yr.
• Body mass index >21 kg · m-2

Exclusion Criteria:

• Pregnant or breastfeeding women
• Subjects unwilling or unable to comply with approved contraception measures
• Subjects unable to give voluntary informed consent
• Subjects on anticoagulant drugs, anemic or with known bleeding diatheses
• Subjects with a history of severe, uncontrolled hypertension, heart disease, cerebrovascular incidents
• Current tobacco use
• Subjects with any known allergies to any of the study medications being used

Physical Exam Exclusion Criteria

• Uncontrolled severe hypertension (i.e., blood pressure greater than 160/100)
• Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmia)
• Pneumonia treatment or hospitalization within 2 weeks prior to enrollment (study visit)
• Hepatic failure / jaundice
• Renal failure
• Cerebrovascular accident occurrence or hospitalization within 4 weeks prior to enrollment
• Fever greater than 38.0 degrees C

Screening Laboratory Tests Exclusion Criteria

• Hematocrit lower than 32 %
• White blood cell (WBC) count lower than 3 thou/ul or greater than 14 thou/ul
• Liver function tests: serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) greater than twice upper limit of normal range
• Alkaline phosphatase greater than 150U/L
• Total bilirubin (TBil) greater than 2 mg/dl
• Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2
• Positive human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
• Any abnormal cardiac response during multi-stage exercise test (if over 40 years of age)