Development of a spontaneously beating vein by cardiomyocyte transplantation in the wall of the inferior vena cava in a rat: A pilot study

PurposeThis study was conducted to determine whether it is feasible to develop a vein that rhythmically beats by implanting immature cardiomyocytes in its wall.MethodsNeonatal cardiomyocytes (5 × 106 cells each) were transplanted into the wall of the inferior vena cava in six female Fischer rats; in six rats, only the medium was transplanted. At 3 weeks after transplantation, the grafted site of the inferior vena cava was exposed and videotaped, and then processed for histology.ResultsDistinct rhythmic beating of the vena cava at the site of cell injection (at a rate lower than aortic beating) was observed in all six rats treated with neonatal cardiomyocyte injections, but in none of the six that received the medium. The vena cava continued to beat spontaneously and rhythmically after the aortas were clamped and after the heart was excised. The beating was manifest by visual contraction and relaxation of the vessel wall. The spontaneous beating rate was 101 ± 7 beats/min at 1 to 3 minutes after excision of the heart. Hematoxylin and eosin staining showed viable grafts in the wall of the vena cava in all that were implanted with neonatal cardiac cells; but in none of the vena cava that received the medium. Neonatal cardiomyocytes in the graft matured with cross striations and stained positive for the muscle marker sarcomeric actin.ConclusionsThe present study demonstrates that neonatal cardiomyocytes survive, mature, and spontaneously and rhythmically contract when implanted in the wall of a vein.

Clinical RelevanceVenous thrombosis occurs in approximately 0.1% of the general population each year in the United States. The interaction between vascular endothelium and platelets plays a key role in the thrombotic event. Pulsatility has been hypothesized to affect the function of vascular endothelium and platelet adhesion. Our present study demonstrates that engrafted neonatal cardiac cells within the wall of the rat inferior vena cava survive, develop an adult phenotype, and exhibit spontaneous beating. This model provides a useful experimental approach to investigate the effect of venous pulsatility on the vascular endothelial behavior in vivo and to determine whether pulsatility prevents platelet adhesion to endothelium in venous stasis and, ultimately, protects against venous thrombosis.