The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction

The epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of cardiosphere-derived cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72 h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 min. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.

Epicardial Delivery of Cardiosphere Derived Cells or Their Extracellular Vesicles in a Relevant Infarcted Swine Model: Safe, Easy but of Limited Effectiveness.

The epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of Cardiosphere-Derived Cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 minutes. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.

Repair of contained ventricular rupture with infected intrapericardial thrombus

Ischemia-mediated ventricular rupture is a rarely encountered process in the era of early percutaneous revascularization. Contained rupture, or pseudoaneurysm often occurs as a result of pericardial adhesions. Even more uncommon is the presence of associated infection involving the rupture. We present the case of a patient with an infected intrapericardial thrombus in the setting of a left ventricular free wall rupture who underwent successful repair.

Effects of mesenchymal stem cell and amnion membrane transfer on prevention of pericardial adhesions

BackgroundTo investigate and compare the antiadhesive/antifibrotic effects of mesenchymal stem cells (MSC) and amnion membrane transfer (AMT) in a rat model.Material and methodsThree experimental and sham groups were formed using 30 Wistar-Albino rats. AMT and MSC were applied to the related groups. The control group was not treated. After 12 weeks follow-up, intracardiac blood and cardiac-pericardiac tissue samples were taken. The severity of adhesions and fibrosis were scored macroscopically and microscopically with Hematoxylin/Eosin and Masson’s trichrome staining. TNF-α, TGF-β, IL-1, PDGF, FGF, VEGF and Caspase-3 levels were measured with the ELISA method.ResultsSevere adhesions were observed in the AMT and control groups, but no adhesion was present in the MSC group. Pericardial thickness, increased vascularity, fibrosis, and collagen accumulation were similar between control and AMT groups, but were less in Sham and MSC groups. Between MSC and AMT groups, only Caspase-3 level was different, which is an apoptosis marker.ConclusionThe positive effects of MSC on adhesion, which we achieved in our study, suggest that it may prevent adhesion. AMT did not provide a positive effect. The correlation of Caspase-3 with postoperative adhesion/fibrosis should be examined in more detail.

Decrease in VEGF-Induced Pericardial Adhesion Formation Using Bevacizumab After Surgery

Objectives. Some degrees of postoperative cardiac adhesions occur in response to the first cardiac surgery in patients that may limit surgeons for subsequent operations and increase the risk of heart injury. In this article, we established a model of postoperative pericardial adhesions, and because vascular endothelial growth factor (VEGF) seems to initiate adhesion formation through inflammatory responses, we used an anti-VEGF antibody, that is, bevacizumab, to examine its effects on postoperative adhesion formation. Methods. Twenty Wistar rats were divided in 2 groups: control and bevacizumab. After chest opening, pericardial sac was opened and the heart was fully exposed. In the bevacizumab group, bevacizumab (2.5 mg/kg) was applied locally on the heart and then the chest was closed. The control group received saline solution as placebo. After 42 days, high-sensitivity C-reactive protein in peripheral blood was measured, and re-sternotomy was performed to measure severity of pericardial adhesions. Then, the hearts were collected from all rats to evaluate percentage of CD-31-positive cells (as a marker of angiogenesis) using immunohistochemical staining. Results. When the bevacizumab group was compared with the control group, we found that the mean score of adhesion (0.89 ± 0.38 vs 2.56 ± 0.41) and CD-31 expression (27.45 ± 3.75% vs 56.26 ± 1.98%) was decreased significantly after bevacizumab administration. However, we did not find any difference in high-sensitivity C-reactive protein levels of control and bevacizumab animals. Conclusion. In the current study, bevacizumab administration could effectively reduce adhesion formation after first sternotomy by preventing VEGF-induced angiogenesis through CD-31 downregulation.