Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: implications for cellular cardiomyoplasty

Abstract

Objective: 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 microm) were carried out in both small and large animal models. The hearts of Lewis rats (250-350 g) received 3 x 10(6) microspheres injected into the left ventricular myocardium. Rats were divided evenly between two experienced operators. The nonbeating (n = 2) and beating (n = 5) hearts of piglets (7.5-7.8 kg) received 3 x 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% +/- 4.05% vs 5.44% +/- 5.66% vs 8.83% +/- 3.29%). There were no significant operator-dependent differences. The retention rates in beating porcine hearts were higher than those in the rats (P < .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.