Improving Right Ventricular Function in Young Adults Born Preterm
Condition: Infant,Premature
MeSH terms: Premature Birth
Intervention: Pulmonary Function Testing; Electrocardiogram; Cardiac Magnetic Resonance Imaging; Metoprolol; Sildenafil
Intervention description: Subjects will undergo spirometry, Plethysmography, and diffusion capacity.; Subjects will undergo an electrocardiogram to ensure sinus rhythm; Subjects will undergo positron magnetic resonance imaging to detect images of the heart; Subjects will receive intravenous metoprolol. Dose titrated 1-5 mg every 2 minutes to achieve goal heart rate of 55-65 beats per minute, or for subjects with a resting heart rate already at goal, titrated to achieve a 10-15% reduction in heart rate.; Subjects will receive a 50 milligram tablet of sildenafil (to be taken orally)
Intervention MeSH terms: Metoprolol; Sildenafil Citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given sildenafil in between imaging scans at one visit, and will receive intravenous metoprolol in between scans at a separate visit. These visits can occur in either order. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out.
Masking: Single (Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: premature adults; premature; premature cardiac function; MRI; sildenafil; metoprolol; CMR

Summary:

      The purpose of this research is to evaluate the short-term effects of sildenafil and
      metoprolol on heart function in young adults born premature.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated informed consent form

          2. Male or female aged 18-35

          3. History of preterm birth (either a or b):

               1. Participant in the Newborn Lung Project (birth year 1988-1991, birth weight <1500
                  g)

               2. Non-NLP participant, with birth weight <1500 g and gestational age 32 weeks or
                  less, verified by medical records

        Exclusion Criteria:

          1. Pregnant or lactating

          2. Use of prescribed medications that would interfere with study medications

               1. Sildenafil: Use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil,
                  vardenafil), nitrates, soluble guanylate cyclase inhibitor (riociguat) within 48
                  hours of study visit

               2. Metoprolol: Use of nodal blocking agents including beta blockers,
                  non-dihydropyridine calcium channel blockers (i.e. diltiazem), and
                  anti-arrhythmics (i.e. amiodarone)

          3. Presence of known comorbidities for which these therapeutic interventions would be
             contraindicated:

               1. Moderate to severe heart failure

               2. Severe bradycardia (heart rate <45), or second or third-degree heart block

               3. Systolic blood pressure <90 mmHg or >190 mmHg

               4. Angina

               5. Severe peripheral arterial circulatory disorders

               6. History of severe bronchospasm

          4. Presence of any implanted device incompatible with CMR imaging

          5. Known allergic or hypersensitivity reaction to components of the study medications

          6. Any other reason for which the investigator deems a subject unsafe or inappropriate
             for study participation.