Procedures are in place for protecting against or minimizing the risks to the healthy volunteers recruited for this study. Physical risk to volunteers and matched related donors will be protected through health screening to determine study eligibility, and medical monitoring with an established test termination criterion during the exercise and isoproterenol infusion trials.
To protect against the remote risk of an adverse cardiac event occurring during exercise and isoproterenol infusion, the study will only enroll volunteers who are considered "low risk" for maximal stress testing in accordance with the guidelines published by the American College of Sports Medicine (ACSM) and American Heart Association (AHA). Individuals who are considered "low risk" are men and women who are asymptomatic and have no more than one risk factor for cardiovascular disease (CVD). The risks to subjects are therefore extremely low. All infusions will take place in the Clinical and Translational Sciences Research Center (CATS) Infusion Suite, which is a designated University of Arizona campus facility for infusion trials and equipped with appropriate medical personnel and monitoring equipment (i.e. ECG). The graded exercise tests and isoproterenol infusions procedures will be performed under the direction of a licensed and board-certified cardiologist
Inclusion Criteria:
Participants must:
- Be between 21 and 55 years of age.
- Be classified as 'low-risk' for graded exercise/stress testing according to ACSM-AHA criteria.
- Have no contraindications for the use of isoproterenol, carvedilol, bisoprolol, nadolol, or roflumilast as per FDA guidelines.
Exclusion Criteria:
Participants will be excluded if they:
- Currently use tobacco products or have quit within the last 6 months.
- Have a body mass index (BMI) greater than 34 kg/m² or waist circumference exceeding 102 cm for men and 88 cm for women.
- Use any medications known to affect the immune system or regularly take ibuprofen/aspirin, antidepressants, or medications that alter blood pressure or cardiovascular function.
- Use of hormone replacement therapy.
- Are pregnant or breastfeeding.
- Have chronic or debilitating arthritis or have been bedridden in the past three months.
- Experienced a common illness (e.g., colds) within the past 6 weeks.
- Have central or peripheral nervous disorders, a history of stroke, or major affective disorder.
- Are infected with HIV or hepatitis or have any autoimmune disease.
- Have known cardiovascular disease or contraindications for the use of isoproterenol, carvedilol, bisoprolol, nadolol, or roflumilast.
- Use any prescription medications or have an allergy to beta-blockers.
- Have a resting heart rate of less than 50 beats per minute.
- Suffer from asthma, emphysema, bronchitis, kidney disease, pheochromocytoma, diabetes, overactive thyroid, or a history of severe anaphylactic reactions.
- Are scheduled for surgery.
Additionally, participants who meet the inclusion criteria but present with more than one of the following cardiovascular disease (CVD) risk factors will be excluded unless cleared by a cardiologist:
- Family History: Myocardial infarction, coronary revascularization, or sudden death before 55 years of age in a father or male first-degree relative, or before 65 years of age in a mother or female first-degree relative.
- Hypertension: Systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg.
- Dyslipidemia: Total serum cholesterol exceeding 200 mg/dl.
- Pre-diabetes: Fasting blood glucose levels between 100 mg/dl and 126 mg/dl.