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Publication Date

11-20-2015

Keywords

heart surgery, sinus node dysfunction, atrial fibrillation, stem cells, animal model

Abstract

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs.

Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of this technique, and to evaluate the acute retention of the delivered cells.

Methods: All in vivo animal experimentation was approved by the University of Wisconsin Animal Care and Use Committee and took place in the Cardiovascular Physiology Core Facility at UW-Madison. MSC (3-5×106 in 50 μl per site) were injected intramyocardially during an open-chest procedure in anesthetized pigs. To track the cells in vivo, MSC were labeled with 18FDG then visualized at 1 and 6 hours postinjection by PET/CT. Pigs were monitored for intraoperative arrhythmia, bleeding and hypotension.

Results: By gently repositioning the heart, both atria were accessible for the injections. The thickest part of each atrium was isolated and stabilized briefly for the injection using a hemostat. The injected cells were visible by PET/CT 1 and 6 hours postinjection. However, when the MSC were labeled with 10mCi 18FDG, the signal was too high, causing a bloom around the areas of injection. So the dose was lowered to 5mCi 18FDG, which resulted in a clear signal at 1 hour in both atria. At 6 hours, the right atrial injection was still easy to read, but the left injection was difficult to resolve from background signal. All injections resulted in cell leakage from the injection site and uptake of the signal into the lungs. However, pulmonary function as measured by SpO2 and EtCO2 was unchanged. Intraoperative arrhythmias detected during the injections were caused by manipulation of the heart. No additional arrhythmias were detected. No bleeding or hypotension was observed as a result of the injections.

Conclusion: This pilot study demonstrated that atrial delivery of MSC is feasible and safe in an open-chest porcine model and that MSC are retained for at least 6 hours postinjection. Subsequent studies will determine the ability of MSC to downregulate inflammation, decrease scarring and prevent sinus node dysfunction.

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