RESUMO
OBJECTIVE: Mesenchymal stromal cells have important immunomodulatory and neuroprotective properties. The aim of this study was to evaluate the feasibility of mesenchymal stromal cell administration into a cardiopulmonary bypass (CPB) circuit, including a pediatric oxygenator, and to assess the immunomodulatory response of the circulating blood prime. METHODS: A bypass circuit with a pediatric oxygenator, including integral filter was primed with bank whole blood. Normal saline (control) or 120 × 106 mesenchymal stromal cells were injected into the venous reservoir after 80 minutes of perfusion. To assess oxygenator function, immune reaction, and cytokine/chemokine levels, the ex vivo circulation was maintained for 300 minutes after administration. RESULTS: There were no differences in flow rate, trans-oxygenator pressure gradient, blood oxygen, and carbon dioxide levels between control and cell delivery groups. No adhesion of mesenchymal stromal cells was observed on the filter mesh by scanning electron microscopy. Lymphocyte surface marker assay found no difference in the number of B cells, T cells, or natural killer cells between the 2 groups, indicating no immunogenicity of allogeneic mesenchymal stromal cells under ex vivo CPB conditions. CPB significantly changed the level of interleukin (IL) 4, IL-6, IL-8, IP-10, macrophage colony stimulating factor, macrophage inflammatory protein-1ß, monocyte chemoattractant protein-1, and IL-1α over time. IL-6 level was significantly increased after cell administration. CONCLUSIONS: The administration of mesenchymal stromal cells does not interfere with oxygenator function. Allogeneic mesenchymal stromal cells show no immunogenicity, and increase plasma IL-6 level during ex vivo circulation. Further investigation is necessary to determine the effect of mesenchymal stromal cell delivery through CPB during pediatric cardiac surgery.
RESUMO
BACKGROUND: Heart failure is a leading cause of death but very little is known about right ventricular (RV) failure (RVF) and right ventricular recovery (RVR). A robust animal model of reversible, RVF does not exist, which currently limits research opportunities and clinical progress. We sought to develop an animal model of reversible, pressure-overload RVF to study RVF and RVR. MATERIALS AND METHODS: Fifteen New Zealand rabbits underwent implantation of a fully implantable, adjustable, pulmonary artery band. Animals were assigned to the control, RVF, and RVR groups (n = 5 for each). For the RVF and RVR groups, the pulmonary artery bands were serially tightened to create RVF and released for RVR. Echocardiographic, cardiac magnetic resonance imaging, and histologic analysis were performed. RESULTS: RV chamber size and wall thickness increased during RVF and regressed during RVR. RV volumes were 1023 µL ± 123 for control, 2381 µL ± 637 for RVF, and 635 µL ± 549 for RVR, and RV wall thicknesses were 0.98 mm ± 0.12 for controls (P = 0.05), 1.72 mm ± 0.60 for RVF, and 1.16 mm ± 0.03 for RVR animals (P = 0.04), respectively. Similarly, heart weight, liver weight, cardiomyocyte size, and the degree of cardiac and hepatic fibrosis increased with RVF and decreased during RVR. CONCLUSIONS: We report an animal model of chronic, reversible, pressure-overload RVF to study RVF and RVR. This model will be used for preclinical studies that improve our understanding of the mechanisms of RVF and that develop and test RV protective and RVR strategies to be studied later in humans.
