Pulsatile Perfusion Therapy Phase II (PPT2)

Inclusion Criteria: Aged 18 to 40 years Non-tobacco/nicotine users (e.g., cigarettes (including electronic cigarettes), chewing tobacco, nicotine gum or patches) Systolic arterial pressure <140 mmHg; diastolic arterial pressure <90 mmHg Normal 12-lead ECG (reviewed by a physician) Normal clinical results from a medical exam reviewed by a board certified physician (e.g., General Health Questionnaire - see attached document) Easily visualized internal carotid and vertebral arteries (via Doppler ultrasound) for accurate measurement of velocity and diameter. Body mass index (BMI) <30 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2); this criteria is used to ensure subjects will fit inside the LBNP chamber Females only: documentation of a negative pregnancy test prior to the familiarization and experimental sessions Exclusion Criteria: Age <18 or >40 years Use of tobacco/nicotine within the last 6 months (e.g., cigarettes (including electronic cigarettes), chewing tobacco, nicotine gum or patches) Body mass index (BMI) >30 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2) Not abstaining from the following 24 hours prior to the experimental session: exercise, alcoholic substances, prescription or non-prescription medications (unless cleared by the medical screener), dietary supplements, herbal medications, caffeinated substances (including coffee, tea (iced or hot), caffeinated energy drinks or sodas). Inability to visualize the internal carotid and vertebral arteries (via Doppler ultrasound) for accurate measurement of velocity and diameter. Positive pregnancy test Post-menopausal females Females with an erratic/irregular menstrual cycle Use of prescription drugs, non-prescription drugs or herbal medicines known to alter cardiovascular, autonomic, or cerebrovascular function unless cleared prior to the study Use of anti-hypertensive medications Use of beta blockers Frequent use of bronchodilators (occasional use, i.e. seasonally, is allowable) Use of anti-coagulant therapy Use of non-contraceptive related hormone therapy Current or past history of hyperthyroidism, or other thyroid hormone-related disease Signs of cardiovascular abnormalities (e.g., resting systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg; abnormal 12-lead ECG) History of cerebrovascular abnormalities (e.g., prior stroke, transient ischemic attacks, epilepsy) Known history of atherosclerosis of the carotid arteries (i.e., plaque formation) History of concussion and or other loss of consciousness within the preceding month Autonomic dysfunction (e.g., Shy-Drager Syndrome, Bradbury-Eggleston syndrome, sinus arrhythmia, idiopathic orthostatic hypotension, fainting disorder) Respiratory illnesses (e.g., chronic asthma (including exercise-induced asthma), Chronic Obstructive Pulmonary Disease, Reactive Airway Disease) History of anaphylaxis Known allergies to medications or other substances (e.g. latex) unless cleared prior to the study History of pre-syncopal/syncopal episodes or orthostatic hypotension Donated blood within the last 60 days History or family history of abnormal blood clotting, clots in deep veins in the legs or pelvis, or blood clots to the lungs aa) Known or suspected abdominal hernia bb) History of alcohol or drug abuse which inhibits the subject's ability to complete this study cc) Known depression, anxiety, or any other mental health issue which inhibits the subject's ability to complete this study dd) Known claustrophobia ee) Previous positive diagnosis of COVID-19