Transplantation of Autologously Derived Mitochondria Following Ischemia

Autologous mitochondria will be delivered to the ischemic heart muscle in one of two ways,
during clinically indicated surgical procedure or during clinically indicated cardiac
catheterization.

For surgical re-operation subjects:

After the subject's chest is open, 1-2 6mm biopsies will be collected from the exposed
skeletal muscle of the chest wall. The tissue will be processed at bedside to extract the
autologous mitochondria. Surgery will proceed as clinically indicated. Prior to closure of
the chest, autologous mitochondria will be injected via 5-10 injections of approximately 0.1
mL each to the damaged area (if damaged muscle is local) or via injection into the proximal
aorta while cross-clamped for clinically indicated surgery for global distribution of
mitochondria via the coronary arteries if there is no evident area of damage. Following
completion of surgical maneuvers the mitochondria will be injected into the aorta and the
cross-clamp will be removed. If there is global injury but a cross-clamp is not clinically
indicated, direct injection into the myocardium will occur throughout the ventricle as
previously described. Chest closure will then occur as and if clinically indicated for both
techniques.

For catheterization subjects:

Once in the catheterization lab, the temporary chest closure will be removed and 1-2 6 mm
biopsies will be collected from the exposed skeletal muscle of the chest wall by the cardiac
surgery team. The tissue will be processed at bedside to extract the autologous mitochondria.
The catheterization will proceed as clinically indicated. Prior to completion of the
procedure (interventional to restore blood flow or hemodynamics), mitochondria will be
infused in 5 mL of buffer as conducted in large animal studies (5) via intracoronary infusion
followed by a 5 mL flush with normal saline. Total dose of mitochondria will be equal to
direct injection subjects, with a larger dilution to allow to infusion via cardiac catheter.

If there is no marked improvement in ventricular function following the injection/infusion of
autologous mitochondria and the subject has a clinically indicated procedure in the days
following the initial delivery, a second injection/infusion will be completed. At this time
the follow up schedule will be reset to Day 0.

Inclusion Criteria:

- Pediatric cardiology patients under the age of 18 on ECMO

- concerns for ischemic injury on the Cardiac Intensive Care Unit

Exclusion Criteria:

- Known mitochondria disorders