CO as a Stimulant for Mitochondrial Biogenesis in Human Cardiac Muscle
| Status: | Terminated |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 20 - Any |
| Updated: | 5/20/2016 |
| Start Date: | February 2014 |
| End Date: | March 2016 |
Effects of Low Level Carbon Monoxide Preconditioning on Human Mitochondrial Biogenesis in Aortic Valve Surgery Patients
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.
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.
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.
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.
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.
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