Beating and arrested intramyocardial injections are associated with significant mechanical loss: implications for cardiac cell transplantation.
BACKGROUND
Cellular cardiomyoplasty is emerging as a potentially novel therapeutic option for heart failure and typically involves direct intramyocardial injection of donor cells into a beating heart. Yet, limited rates of cell engraftment remain an obstacle to be overcome before cell therapy is fully recognized. Mechanical and biological mechanisms may account for observed donor cell loss. This study examines acute mechanical loss during intramyocardial injections in beating and arrested hearts.


METHODS
A porcine cardiopulmonary bypass model was used. Animals underwent either beating (n = 5) or arrested (n = 5) intramyocardial injections into the left ventricle. Fluorescent microspheres were used in lieu of cells because they are biologically inert. Thirty minutes after delivery, animals were euthanized. Microspheres in cardiac and peripheral tissues were quantified using flow cytometry.


RESULTS
Approximately 10% of microspheres were retained within the site of injection in both groups. There was no statistical difference between microsphere retention rates in either the beating or the arrested heart group. Microspheres were found in peripheral organs, pericardial fluid, and the delivery device.


CONCLUSIONS
The majority of microspheres injected intramyocardially are lost in both beating and arrested hearts. Cardiac standstill does not enhance microsphere retention. Possible mechanisms include leakage from the injection site and washout via the cardiac venous/lymphatic system. Delivery strategy will need to be modified if more cells are to be retained within the target organ.
Hudson
Wes
W
Division of Cardiothoracic Surgery, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Collins
Maria C
MC
deFreitas
Dorian
D
Sun
You S
YS
Muller-Borer
Barbara
B
Kypson
Alan P
AP
D000818:Animals; D018421:Cardiomyoplasty; D002315:Cardiopulmonary Bypass; D017690:Cell Transplantation; D005260:Female; D005453:Fluorescence; D006321:Heart / Q000502:physiology*; D006324:Heart Arrest, Induced; D006352:Heart Ventricles; D007267:Injections; D008297:Male; D008863:Microspheres; D023421:Models, Animal; D009200:Myocardial Contraction; D034421:Sus scrofa