Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty (original) (raw)

2006, The Journal of Thoracic and Cardiovascular Surgery

Direct intramyocardial injection is a common route of donor cell administration for myocardial cell therapy. Studies have demonstrated a significant and rapid loss of implanted cells, which is thought to be biologically caused. We hypothesized that mechanical loss of cells from the contracting myocardium might actually be the main culprit. Methods: Intramyocardial injections of fluorescent microspheres (10 m) were carried out in both small and large animal models. The hearts of Lewis rats (250-350 g) received 3 ϫ 10 6 microspheres injected into the left ventricular myocardium. Rats were divided evenly between two experienced operators. The nonbeating (n ϭ 2) and beating (n ϭ 5) hearts of piglets (7.5-7.8 kg) received 3 ϫ 10 6 microspheres. The hearts were excised within 10 minutes, and the microspheres retained in the myocardium were quantified with fluorescent flow cytometry. Results: In the beating-heart rat model, the microsphere retention rates after a single injection were similar with and without purse-string occlusion of needle puncture sites and slightly lower than after multiple site injections (6.19% Ϯ 4.05% vs 5.44% Ϯ 5.66% vs 8.83% Ϯ 3.29%). There were no significant operatordependent differences. The retention rates in beating porcine hearts were higher than those in the rats (P Ͻ .05) but markedly lower than those in nonbeating porcine hearts (11.1% vs 67.4%). Conclusion: Mechanical leakage and washout may account for a major portion of cell loss after cell implantation, and efforts aimed at reducing mechanical loss in the beating heart may yield a greater benefit than those targeting biologic loss alone. S urvival of cells after intramyocardial injection is crucial to the efficacy of therapeutic cell transplantation. In an attempt to increase the number of cells surviving after injection, many researchers have targeted cell deaths (due to apoptosis, ischemia, free radical formation, etc). However, recent studies suggest a massive loss of cells in the first minutes after injection. 1-4 In light of the early time frame in which this loss takes place, it is unlikely to be accounted for solely by cell death. Cells can be delivered in a variety of ways, and one of the most common methods is direct intramyocardial injection. The technique of injection may result in mechanical loss, in the form of cells leaking from the site through the puncture hole, cells retained in the syringe, or vascular washout. Because the heart differs from other organs in that it is constantly contracting, it is possible that this may contribute to the mechanical loss by squeezing the injected cells out of the myocardium. As a result, the cells retained in the myocardium immediately postinjection represent only a fraction of those initially implanted. It is from this subset that biologic loss and gain, through cell death and proliferation, can then affect the quantity of surviving cells.