: Vascular Function in Health and Disease

• Status: Recruiting
• Trial end date: 2025-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Many control mechanisms exist which successfully match the supply of blood with the metabolic demand of various tissues under wide-ranging conditions. One primary regulator of vasomotion and thus perfusion to the muscle tissue is the host of chemical factors originating from the vascular endothelium and the muscle tissue, which collectively sets the level of vascular tone. With advancing age and in many disease states, deleterious adaptations in the production and sensitivity of these vasodilator and vasoconstrictor substances may be observed, leading to a reduction in skeletal muscle blood flow and compromised perfusion to the muscle tissue. Adequate perfusion is particularly important during exercise to meet the increased metabolic demand of the exercising tissue, and thus any condition that reduces tissue perfusion may limit the capacity for physical activity. As it is now well established that regular physical activity is a key component in maintaining cardiovascular health with advancing age, there is a clear need for further studies in populations where vascular dysfunction is compromised, with the goal of identifying the mechanisms responsible for the dysfunction and exploring whether these maladaptations may be remediable. Thus, to better understand the etiology of these vascular adaptations in health and disease, the current proposal is designed to study changes in vascular function with advancing age, and also examine peripheral vascular changes in patients suffering from chronic obstructive pulmonary disease (COPD), Sepsis, Pulmonary Hypertension, and cardiovascular disease. While there are clearly a host of vasoactive substances which collectively act to govern vasoconstriction both at rest and during exercise, four specific pathways that may be implicated have been identified in these populations: Angiotensin-II (ANG-II), Endothelin-1 (ET-1), Nitric Oxide (NO), and oxidative stress.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Russell Richardson
• Treatments: Acetylcholine; Angiotensin II; Angiotensinogen; cyclo(Trp-Asp-Pro-Val-Leu); Fexofenadine; Giapreza; Nitroprusside; Norepinephrine; Phentolamine; Ranitidine; Thioctic Acid; Valsartan; Vitamin E; Vitamins

Criteria

Inclusion Criteria:

• Healthy Young Volunteers: 18-30 years of age with no diseases or conditions that would affect their participation in the study

• Healthy Older Controls: volunteers 65 years of age or older with no diseases or conditions that would affect their participation in the study

• Coronary Angiography subjects: patients undergoing routine coronary angiography

• Chronic Obstructive Pulmonary Disease subjects: patients diagnosed with mild to moderate COPD

• Pulmonary Arterial Hypertension subjects: patients with idiopathic or heritable Group 1 pulmonary arterial hypertension

• Heart Failure subjects: patients with Class I, II or III New York Heart Association symptoms of Heart Failure

• Hypertension subjects: patients diagnosed with chronic high blood pressure

Exclusion Criteria:

• Severe COPD (use of supplemental oxygen, or have a one-second forced expiratory volume of less than 30% predicted)

• History of myocardial infarction

• History of percutaneous coronary revascularization

• History of coronary artery bypass grafting

• Unstable angina pectoris

• History of variant angina

• Ejection fraction < 50%

• Significant renal disease (Glomerular Filtration Rate < 50 mL/min/1.73m2)

• Subjects whose medical care or safety may be at risk from undergoing a Magnetic Resonance Imaging examination (e.g. pacemaker, metal implants, certain types of heart valves)

• Subject is pregnant

• Subject has physical ailments (other than COPD, PAH, HF, or hypertension) that would prevent them from study participation in the judgment of the investigator