Red Blood Cell ATP Release and Vascular Function in Humans
Condition: Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      Previous work demonstrates that the red blood cells of older adults do not release a potent
      vasodilator (ATP) as well as the red blood cells of younger adults. The investigators are
      targeting a pathway within the red blood cell using fasudil hydrochloride to determine if
      both the release of ATP from red blood cells and blood flow responses to low oxygen (hypoxia)
      and exercise in older adults can be improved.
    

Detailed description: 
      Participants will initiate contact with the investigators by responding to flyers placed in
      the community either by phone or email. The first correspondence (phone or email) will
      provide a brief description of the research and ask a series of screening questions to
      determine age, height, weight, and any medications participants may be taking as well as the
      current health status (diagnoses, basic health history, and physical activity level) of
      participants. If they qualify, a two hour screening visit is scheduled during a time when the
      participant will be examined by the physician. All participants will undergo informed consent
      in a face to face private meeting with the research coordinator. Following informed consent,
      participants will be evaluated by a physician and undergo a treadmill stress test to rule out
      cardiovascular disease.

      During the study, heart rate will be monitored with a 3-lead ECG and blood pressure will be
      monitored noninvasively with a blood pressure cuff on the finger (finometry). Venous blood
      will be collected at multiple time points via a catheter inserted into a forearm vein
      draining skeletal muscle circulation for measurement of blood gases (0.5 mL/sample) and
      plasma [ATP] (2 mL/sample), with less than 100 mL of blood being drawn in total (~60mL
      total). Blood flow at rest and in response to hypoxia and exercise will be measured
      non-invasively using Doppler ultrasound of the brachial artery. Hypoxia trials will be
      performed by having participants breathe a low oxygen gas mixture via a mouthpiece that is
      hooked up to gas tanks and an anesthesia monitor to decrease their oxygen saturation to ~80%
      (similar to hiking a 14er) for 10 minutes. Exercise trials will last for approximately 15
      minutes and will involve participants performing graded-intensity rhythmic handgrip exercise
      by lifting weights (corresponding to a low, moderate, and high workload) using a pulley
      system. The drug treatment used in this study (fasudil) is being given because it may improve
      red blood cell ATP release in older adults. This is a double-blinded placebo controlled
      study, thus participation will occur on two randomized experimental days.
    

Intervention name(s): Fasudil Hydrochloride; Saline
Intervention type(s): Drug; Other
Intervention description(s): 10 mg/mL vial of fasudil hydrochloride. 6 mL (60 mg) of fasudil hydrochloride are added to a 100 mL saline bag for delivery to subjects.; 100 mL saline bag.
Other intervention name(s): Placebo
Intervention MeSH terms: Fasudil
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a randomized, double-blind, placebo-controlled, crossover study. Approximately 20 young and 20 older adults will be recruited for participation and randomly assigned to either a placebo (saline) infusion or a fasudil hydrochloride infusion. The dose of fasudil hydrochloride is 60 mg/ 60 min.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science