Heart Disease, Heart Failure With Preserved Ejection Fraction, Exercise Intolerance, Pulmonary Hypertension
Conditions
Brief summary
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that has no proven effective treatment. This study assessed the effects of acute nitrite administration on resting and exercise hemodynamics in patients with HFpEF.
Detailed description
Subjects were studied on their long-term medications in the post-absorptive state and supine position. Right heart catheterization was performed with simultaneous expired gas analysis at rest and during supine exercise at a 20 Watts workload for 5 minutes. After the first exercise phase (before any drug administration) and after return to steady-state baseline hemodynamic values, subjects were randomized. Study drug or placebo was infused for 5 minutes. After a 10 minute observation period, hemodynamic measurements were repeated at rest, followed by repeat supine exercise at a 20 Watts workload for 5 minutes, identical to the study's first phase. Arterial and venous blood samples and hemodynamic and expired gas data were acquired during each stage of the protocol.
Interventions
DRUGNitrite
Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure.
DRUGSaline Placebo for Nitrite
Normal saline placebo will be infused for 5 minutes during the cardiac catheterization procedure. Hemodynamics will then be measured at baseline after study drug infusion and again during low level exercise (20 Watts).
Sponsors
Barry Borlaug
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Scheduled to undergo a cardiac catheterization procedure. * Clinical symptoms of shortness of breath and fatigue * Normal left ventricular ejection fraction (≥50%) * Elevated left ventricular filling pressures at cardiac catheterization (defined as resting pulmonary capillary wedge pressure (PCWP)\>15 mmHg and/or PCWP≥25 mmHg during exercise)
Exclusion criteria
* Systolic BP \<120 mmHg * Prior nitrate therapy (within previous 2 weeks) * Glucose 6-phosphate dehydrogenase (G6PD) deficiency * Other non-HFpEF specific causes of heart failure such as significant valvular disease (\>moderate left-sided regurgitation, \>mild stenosis), severe pulmonary disease, unstable coronary disease or coronary spasm, primary renal or hepatic disease, constrictive pericarditis, or infiltrative, restrictive, or hypertrophic cardiomyopathies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Pulmonary Capillary Wedge Pressure (PCWP) | during repeat exercise run, approximately 30 minutes after study drug administration | Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Heart Rate After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) |
| Change in Blood Pressure After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) |
| Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure. |
| Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness. |
| Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. |
| Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection. |
| Change in Oxygen Consumption (VO_2) After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) |
| Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body. |
| Change in Cardiac Output After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) The volume of blood pumped per minute by each ventricle of the heart. Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate. |
| Change in Stroke Volume After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction. |
| Change in Central Pressures After Study Drug (Resting) | baseline, approximately 30 minutes after study drug administration | Values are resting values after receiving study drug minus resting values before study drug (on the same day.) |
| Change in Heart Rate After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) |
| Change in Blood Pressure After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) |
| Change in PVR After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure. |
| Change in PA Compliance After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness. |
| Change in SVR After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. |
| Change in LVSW After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection. |
| Change in Oxygen Consumption (VO_2) After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) |
| Change in Arteriovenous Oxygen Difference After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body. |
| Change in Cardiac Output After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate. |
| Change in Stroke Volume After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction. |
| Change in Central Pressures After Study Drug (Exercise) | baseline, approximately 30 minutes after study drug administration | Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled in the trial between January and September 2014.
Participants by arm
| Arm | Count |
|---|---|
| Nitrite Study drug (NaNO\_2 50 mcg/kg/min) will be infused for 5 minutes during the cardiac catheterization procedure. | 14 |
| Placebo Saline Placebo for Nitrite will be infused for 5 minutes during the cardiac catheterization procedure. | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Nitrite | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 6 | 70 years STANDARD_DEVIATION 8 | 69 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 14 participants | 14 participants | 28 participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.
Time frame: during repeat exercise run, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Exercise Pulmonary Capillary Wedge Pressure (PCWP) | 19.0 mm Hg | Standard Deviation 5 |
| Placebo | Exercise Pulmonary Capillary Wedge Pressure (PCWP) | 28.0 mm Hg | Standard Deviation 6 |
p-value: 0.0003ANCOVA
Secondary
Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting) | 0.4 ml/dl | Standard Deviation 0.5 |
| Placebo | Change in Arteriovenous Oxygen Content Difference After Study Drug (Resting) | 0 ml/dl | Standard Deviation 0.4 |
Comparison: Comparison between the arms for arteriovenous oxygen content difference.p-value: 0.1t-test, 2 sided
Secondary
Change in Arteriovenous Oxygen Difference After Study Drug (Exercise)
Arteriovenous oxygen difference is the difference in the oxygen content of the blood between the arterial blood and the venous blood. It is an indication of how much oxygen is removed from the blood in capillaries as the blood circulates in the body.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Arteriovenous Oxygen Difference After Study Drug (Exercise) | 0.2 ml/dl | Standard Deviation 0.4 |
| Placebo | Change in Arteriovenous Oxygen Difference After Study Drug (Exercise) | 0 ml/dl | Standard Deviation 0.6 |
Comparison: Comparison between the arms for change in arteriovenous oxygen difference after study drug (exercise).p-value: 0.6t-test, 2 sided
Secondary
Change in Blood Pressure After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitrite | Change in Blood Pressure After Study Drug (Exercise) | Diastolic Blood Pressure | -5 mm Hg | Standard Deviation 8 |
| Nitrite | Change in Blood Pressure After Study Drug (Exercise) | Systolic Blood Pressure | -5 mm Hg | Standard Deviation 13 |
| Placebo | Change in Blood Pressure After Study Drug (Exercise) | Systolic Blood Pressure | 2 mm Hg | Standard Deviation 10 |
| Placebo | Change in Blood Pressure After Study Drug (Exercise) | Diastolic Blood Pressure | 0 mm Hg | Standard Deviation 2 |
Comparison: Comparison between the arms for change in systolic blood pressure.p-value: 0.2t-test, 2 sided
Comparison: Comparison between the arms for change in diastolic blood pressure.p-value: 0.05t-test, 2 sided
Secondary
Change in Blood Pressure After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitrite | Change in Blood Pressure After Study Drug (Resting) | Systolic Blood Pressure | -7 mm Hg | Standard Deviation 8 |
| Nitrite | Change in Blood Pressure After Study Drug (Resting) | Mean Blood Pressure | -3 mm Hg | Standard Deviation 4 |
| Placebo | Change in Blood Pressure After Study Drug (Resting) | Systolic Blood Pressure | -2 mm Hg | Standard Deviation 10 |
| Placebo | Change in Blood Pressure After Study Drug (Resting) | Mean Blood Pressure | -1 mm Hg | Standard Deviation 6 |
Comparison: Comparison between the arms for change in systolic blood pressure.p-value: 0.11t-test, 2 sided
Comparison: Comparison between the arms for change in mean blood pressure.p-value: 0.2t-test, 2 sided
Secondary
Change in Cardiac Output After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Cardiac Output After Study Drug (Exercise) | 0.5 L/min | Standard Deviation 0.7 |
| Placebo | Change in Cardiac Output After Study Drug (Exercise) | -0.4 L/min | Standard Deviation 0.7 |
Comparison: Comparison between the arms for change in cardiac output after study drug (exercise).p-value: 0.002t-test, 2 sided
Secondary
Change in Cardiac Output After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) The volume of blood pumped per minute by each ventricle of the heart. Cardiac output is equal to the stroke volume (the amount of blood pumped from a ventricle in a single heartbeat) times the heart rate.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Cardiac Output After Study Drug (Resting) | -0.4 L/min | Standard Deviation 0.8 |
| Placebo | Change in Cardiac Output After Study Drug (Resting) | -0.2 L/min | Standard Deviation 0.5 |
Comparison: Comparison between the arms for change in cardiac output.p-value: 0.4t-test, 2 sided
Secondary
Change in Central Pressures After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitrite | Change in Central Pressures After Study Drug (Exercise) | Right atrial pressure | -5 mm Hg | Standard Deviation 2 |
| Nitrite | Change in Central Pressures After Study Drug (Exercise) | Pulmonary artery systolic pressure | -11 mm Hg | Standard Deviation 6 |
| Nitrite | Change in Central Pressures After Study Drug (Exercise) | Mean pulmonary artery pressure | 10 mm Hg | Standard Deviation 4 |
| Nitrite | Change in Central Pressures After Study Drug (Exercise) | PCWP | -11 mm Hg | Standard Deviation 5 |
| Placebo | Change in Central Pressures After Study Drug (Exercise) | PCWP | -2 mm Hg | Standard Deviation 5 |
| Placebo | Change in Central Pressures After Study Drug (Exercise) | Right atrial pressure | -1 mm Hg | Standard Deviation 2 |
| Placebo | Change in Central Pressures After Study Drug (Exercise) | Mean pulmonary artery pressure | -2 mm Hg | Standard Deviation 5 |
| Placebo | Change in Central Pressures After Study Drug (Exercise) | Pulmonary artery systolic pressure | -4 mm Hg | Standard Deviation 8 |
Comparison: Comparison between the arms for change in right atrial pressure (exercise).p-value: 0.0002t-test, 2 sided
Comparison: Comparison between the arms for change in pulmonary artery systolic pressure (exercise).p-value: 0.01t-test, 2 sided
Comparison: Comparison between the arms for change in mean pulmonary artery pressure (exercise).p-value: 0.0002t-test, 2 sided
Comparison: Comparison between the arms for change in PCWP (exercise).p-value: 0.0002t-test, 2 sided
Secondary
Change in Central Pressures After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitrite | Change in Central Pressures After Study Drug (Resting) | Right atrial pressure | -2 mm Hg | Standard Deviation 2 |
| Nitrite | Change in Central Pressures After Study Drug (Resting) | Pulmonary artery systolic pressure | -8 mm Hg | Standard Deviation 5 |
| Nitrite | Change in Central Pressures After Study Drug (Resting) | Mean pulmonary artery pressure | -6 mm Hg | Standard Deviation 3 |
| Nitrite | Change in Central Pressures After Study Drug (Resting) | PCWP | -3 mm Hg | Standard Deviation 3 |
| Placebo | Change in Central Pressures After Study Drug (Resting) | PCWP | 0 mm Hg | Standard Deviation 1 |
| Placebo | Change in Central Pressures After Study Drug (Resting) | Right atrial pressure | 0 mm Hg | Standard Deviation 1 |
| Placebo | Change in Central Pressures After Study Drug (Resting) | Mean pulmonary artery pressure | -1 mm Hg | Standard Deviation 3 |
| Placebo | Change in Central Pressures After Study Drug (Resting) | Pulmonary artery systolic pressure | -3 mm Hg | Standard Deviation 4 |
Comparison: Comparison between the arms for change in pulmonary artery systolic pressure.p-value: 0.01t-test, 2 sided
Comparison: Comparison between the arms for change in mean pulmonary artery pressure.p-value: 0.002t-test, 2 sided
Comparison: Comparison between the 2 arms for change in PCWP.p-value: <0.0001t-test, 2 sided
Comparison: Comparison between the arms for change in right atrial pressure.p-value: 0.0003t-test, 2 sided
Secondary
Change in Heart Rate After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Heart Rate After Study Drug (Exercise) | -1 beats/minute | Standard Deviation 6 |
| Placebo | Change in Heart Rate After Study Drug (Exercise) | 0 beats/minute | Standard Deviation 3 |
Comparison: Comparison between the arms for change in heart rate.p-value: 0.3t-test, 2 sided
Secondary
Change in Heart Rate After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Heart Rate After Study Drug (Resting) | 0 beats/minute | Standard Deviation 5 |
| Placebo | Change in Heart Rate After Study Drug (Resting) | -3 beats/minute | Standard Deviation 5 |
p-value: 0.15t-test, 2 sided
Secondary
Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting) | -6 g/beat | Standard Deviation 18 |
| Placebo | Change in Left Ventricular Stroke Work (LVSW) After Study Drug (Resting) | 0 g/beat | Standard Deviation 9 |
Comparison: Comparison between the arms for change in LVSW.p-value: 0.3t-test, 2 sided
Secondary
Change in LVSW After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke work refers to the work done by the ventricle to eject a volume of blood (i.e., stroke volume) into the aorta. Ventricular stroke work can be estimated as the product of stroke volume and mean aortic pressure during ejection.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in LVSW After Study Drug (Exercise) | 15 g/beat | Standard Deviation 12 |
| Placebo | Change in LVSW After Study Drug (Exercise) | -2 g/beat | Standard Deviation 8 |
Comparison: Comparison between the arms for change in LVSW after study drug (exercise)p-value: 0.0003t-test, 2 sided
Secondary
Change in Oxygen Consumption (VO_2) After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Oxygen Consumption (VO_2) After Study Drug (Exercise) | 70 ml/min | Standard Deviation 138 |
| Placebo | Change in Oxygen Consumption (VO_2) After Study Drug (Exercise) | -30 ml/min | Standard Deviation 67 |
Comparison: Comparison between the arms for change in oxygen consumption (VO\_2) after study drug (exercise).p-value: 0.02t-test, 2 sided
Secondary
Change in Oxygen Consumption (VO_2) After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.)
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Oxygen Consumption (VO_2) After Study Drug (Resting) | -2 ml/min | Standard Deviation 38 |
| Placebo | Change in Oxygen Consumption (VO_2) After Study Drug (Resting) | -6 ml/min | Standard Deviation 15 |
Comparison: Comparison between the arms for change in VO\_2.p-value: 0.8t-test, 2 sided
Secondary
Change in PA Compliance After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in PA Compliance After Study Drug (Exercise) | 0.8 ml/mm Hg | Standard Deviation 0.9 |
| Placebo | Change in PA Compliance After Study Drug (Exercise) | 0.5 ml/mm Hg | Standard Deviation 0.9 |
Comparison: Comparison between the arms for change in PA compliance after study drug (exercise)p-value: 0.3t-test, 2 sided
Secondary
Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary artery compliance is an index of the elasticity of the blood vessel, an indication of arterial stiffness.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting) | 0.8 ml/mm Hg | Standard Deviation 1.3 |
| Placebo | Change in Pulmonary Artery (PA) Compliance After Study Drug (Resting) | 0.2 ml/mm Hg | Standard Deviation 0.6 |
Comparison: Comparison between the arms for change in pulmonary artery compliance.p-value: 0.1t-test, 2 sided
Secondary
Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting) | -0.3 mm Hg/L/min | Standard Deviation 0.4 |
| Placebo | Change in Pulmonary Vascular Resistance (PVR) After Study Drug (Resting) | -0.4 mm Hg/L/min | Standard Deviation 0.6 |
Comparison: Comparison between the arms for change in PVR.p-value: 0.7t-test, 2 sided
Secondary
Change in PVR After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Pulmonary Vascular Resistance (PVR) is the resistance to flow that must be overcome to push blood through the pulmonary vasculature. Acute and chronic lung disease can both cause an increase in PVR. Chronic PVR can lead to right sided heart failure.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in PVR After Study Drug (Exercise) | 0 mm Hg/L/min | Standard Deviation 0.4 |
| Placebo | Change in PVR After Study Drug (Exercise) | 0.2 mm Hg/L/min | Standard Deviation 0.4 |
Comparison: Comparison between the arms for change in PVR after study drug (exercise)p-value: 0.3t-test, 2 sided
Secondary
Change in Stroke Volume After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Stroke Volume After Study Drug (Exercise) | 7 ml | Standard Deviation 8 |
| Placebo | Change in Stroke Volume After Study Drug (Exercise) | -5 ml | Standard Deviation 6 |
Comparison: Comparison between the arms for change in stroke volume after study drug (exercise).p-value: 0.0002t-test, 2 sided
Secondary
Change in Stroke Volume After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Stroke volume is the amount of blood pumped out of the heart (left ventricle - to the body) during each contraction.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Stroke Volume After Study Drug (Resting) | -5 ml | Standard Deviation 16 |
| Placebo | Change in Stroke Volume After Study Drug (Resting) | -1 ml | Standard Deviation 9 |
Comparison: Comparison between the arms for change in stroke volume.p-value: 0.4t-test, 2 sided
Secondary
Change in SVR After Study Drug (Exercise)
Values are exercise values after receiving study drug minus exercise values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in SVR After Study Drug (Exercise) | -70 dyne/s * cm^5 | Standard Deviation 140 |
| Placebo | Change in SVR After Study Drug (Exercise) | 70 dyne/s * cm^5 | Standard Deviation 100 |
Comparison: Comparison between the arms for change in SVR after study drug (exercise).p-value: 0.007t-test, 2 sided
Secondary
Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting)
Values are resting values after receiving study drug minus resting values before study drug (on the same day.) Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.
Time frame: baseline, approximately 30 minutes after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrite | Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting) | 140 dyne/s * cm^5 | Standard Deviation 350 |
| Placebo | Change in Systemic Vascular Resistance (SVR) After Study Drug (Resting) | 20 dyne/s * cm^5 | Standard Deviation 160 |
Comparison: Comparison between the arms for change in SVR.p-value: 0.3t-test, 2 sided