Assessment of Cardiac Function in Dogs with Doxorubicin-Induced Cardiomyopathy After a Single Intracoronary Stem Cell Transplantation
Stem cell transplantation has been shown to improve cardiac function in several experimental models and even in clinical practice in human beings. These benefits are likely to be the result of several factors, including myocardial neovascularization. In dogs, however, data still lacks about the benefits of stem cell therapy to improve cardiac contractility or relaxation. Therefore, this study was aimed at evaluating how cardiac function performs after a single intracoronary injection of autologous bone marrow-derived stem cells in a group of dogs with doxorubicin-induced cardiomyopathy with moderate systolic and diastolic dysfunction.
Seven mature dogs (1 male; 6 females), with mean weight of 17.4 Kg, were enrolled in the study. Because of chronic doxorubicin therapy, these animal were shown to have moderate systolic and diastolic compromise at baseline, with mean fractional shortening of 19%, mean left-ventricular systolic diameter of 2.92 cm, and mean isovolumic relaxation time of 54.5 msec. Dogs were randomly divided into two groups: G1 with 4 dogs that were given stem cells, and G2 with three dogs that were evaluated as controls. Stem cells were obtained from the bone marrow. Briefly, the marrow was aspirated, centrifuged in Ficoll, washed several times and diluted to permit intracoronary delivery, which was accomplished with a catheter inserted through the femoral artery under fluoroscopy guidance and general anesthesia. Mean stem cell recovery was 22.6%, whereas cellular viability reached 96.2%. At least 60 million cells were delivered into the left coronary artery of each dog. After the procedure, every animal was evaluated for 6 months at monthly intervals. We recorded the left ventricular internal diameter at systole (LVIDs), fractional shortening (FS), ejection fraction (EF), pre-ejection period-to-left ventricular ejection time ratio (PEP/LVET), isovolumic relaxation time (IVRT), and the Tei index of myocardial performance (TEI). An analysis of variance was used to check for significant changes along time. Also, an unpaired T test was used to compare groups at every single moment.
Results are listed in Table 1. One of the dogs that were given stem cells presented unexplained sudden death 12 days after the procedure. In G1, a significant decrease was seen in LVIDs (P=0.0005), PEP/LVET (P=0.0044), IVRT (P=0.0180), and TEI (P=0.0012), as well as a significant increase in FS (P=0.0004), and EF (P=0.0005). On the contrary, G2 not only did not show improvement in the echocardiographic parameters as some of them also worsened during the experimental time.
Results allowed concluding that stem cell transplantation is a feasible technique with promising results in the treatment of canine doxorubicin-induced cardiomyopathy. Further studies are needed to determine what are the benefits of stem cell therapy in a large population of dogs, and well as in animals with idiopathic dilated cardiomyopathy