Carbon Monoxide, Cardiac Disease, Mitochondrial Biogenesis
Conditions
Keywords
cardiac disease, mitochondrial biogenesis, carbon monoxide
Brief summary
This study will test if inhalation of Carbon Monoxide (CO) will increase the numbers of mitochondria in heart muscle. Mitochondria are the small components of muscle and other cells that convert fuel and oxygen to the easily usable forms of energy (ATP) that power all cell's activities. Adequate numbers of healthy mitochondria are essential to heart cell function. From animal and other studies we have reason to believe that breathing small amounts of CO will signal the body to increase the numbers of mitochondria in heart cells. We propose to test this theory in heart valve surgery patients by examining a small sample of heart tissue (from the right atrial appendage) that is routinely cut out during the preparation of the patient for cardio-pulmonary bypass and that would otherwise be discarded by the surgeon. Muscle samples from two groups of subjects will be compared. One group will breath CO and the other group will breath room air. If CO is effective, we should notice an increase in the numbers of mitochondria in the group that was exposed to CO compared to the group that breathed room air.
Detailed description
PURPOSE AND OBJECTIVE: Endogenously produced carbon monoxide (CO) is known to act as a physiologic signaling molecule to induce mitochondrial biogenesis. This study will test if low-level CO preconditioning induces myocardial biogenesis in humans and if clinical benefit is derived from it. STUDY ACTIVITIES AND POPULATION: The study is an interventional, prospective, randomized, double-blinded trial with a 2-week follow up period. Forty subjects will be recruited from the population of patients scheduled to undergo elective aortic valve replacement. For safety purposes patients with coronary disease will be excluded. Subjects meeting the inclusion criteria will be randomized to receive either air or air containing CO @ 200ppm as a one-hour inhalational treatment per day over the course of the three days immediately prior to their scheduled operation. Biochemical markers for mitochondrial biogenesis (blood and right atrial tissue) and clinical outcome parameters ( BUN/creatinine, and left ventricular function measured by 2D echo) will be measured in all patients pre and post-operatively. Right atrial tissue samples will be collected from tissue that is routinely excised during placement of venous cannulas for cardiopulmonary bypass. RISK/SAFETY & DATA ANALYSIS: Risks will be those of CO inhalation and blood drawing. The 200ppm dose chosen is within OSHA work place exposure limits and has been used safely in human subjects previously. Data will be analyzed by comparing biogenetic marker levels and clinical parameters pre and post intervention and control to CO treatment group.
Interventions
DRUG200ppm CO for one hour
This is the study intervention. The treatment group will breath 200 ppm of CO for one hour over the three days immediately prior to surgery.
OTHERControl
This group will breath room air for one hour per day over the course of the three days immediately prior to surgery.
Sponsors
John J Freiberger
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to consent 2. Competent adult 3. Scheduled to undergo aortic or mitral valve surgery only, not combined valve / revascularization procedures.
Exclusion criteria
1. Unable to consent 2. Tobacco use 3. Unanticipated medical diagnoses made at the time of surgery which require further procedures lengthening OR time and complexity above that of AVR alone. 4. Concomitant coronary artery disease. 5. Renal dialysis 6. Hemodynamic instability 7. End stage COPD defined as requiring home oxygen 8. By history any significant exposure to second hand smoke including living with a smoker who smokes indoors or working in a high smoking environment for 8 hours a day or more (i.e. factory or bar) will exclude subject from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Markers for Mitochondrial Biogenesis (Blood and Right Atrial Tissue) | 2 weeks | Right atrial biochemical markers will be measured one time only, intra-operatively. Blood Biochemical markers will be measured before CO exposure and at intervals up to one week post-operatively |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare Blood to Right Atrial Tissue Biochemical Markers of Mitochondrial Biogenesis | on week | Biochemical markers in both right atrial tissue and blood will be measured and compared to see if the more easily obtained blood markers accurately describe changes expected in the heart. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group This group will breath room air for one hour per day over the course of the three days immediately prior to surgery.
Control: This group will breath room air for one hour per day over the course of the three days immediately prior to surgery. | 0 |
| CO Group This group will breath 200 ppm of CO for one hour per day over the course of the three days immediately prior to surgery.
200ppm CO for one hour: This is the study intervention. The treatment group will breath 200 ppm of CO for one hour over the three days immediately prior to surgery. | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | — Participants |
| Age, Categorical >=65 years | — Participants |
| Age, Categorical Between 18 and 65 years | — Participants |
| Sex: Female, Male Female | — Participants |
| Sex: Female, Male Male | — Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Biochemical Markers for Mitochondrial Biogenesis (Blood and Right Atrial Tissue)
Right atrial biochemical markers will be measured one time only, intra-operatively. Blood Biochemical markers will be measured before CO exposure and at intervals up to one week post-operatively
Time frame: 2 weeks
Population: Molecular data was not collected for the single enrolled participant.
Secondary
Compare Blood to Right Atrial Tissue Biochemical Markers of Mitochondrial Biogenesis
Biochemical markers in both right atrial tissue and blood will be measured and compared to see if the more easily obtained blood markers accurately describe changes expected in the heart.
Time frame: on week
Population: Molecular data was not collected for the single enrolled participant.