Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis.

BACKGROUND: We recently demonstrated that epicardial progenitor cells participate in the regenerative response to myocardial infarction (MI) and factors released in the pericardial fluid (PF) may play a key role in this process. Exosomes are secreted nanovesicles of endocytic origin, identified in most body fluids, which may contain molecules able to modulate a variety of cell functions. Here, we investigated whether exosomes are present in the PF and their potential role in cardiac repair. METHODS AND RESULTS: Early gene expression studies in 3day-infarcted mouse hearts showed that PF induces epithelial-to-mesenchymal transition (EMT) in epicardial cells. Exosomes were identified in PFs from non-infarcted patients (PFC) and patients with acute MI (PFMI). A shotgun proteomics analysis identified clusterin in exosomes isolated from PFMI but not from PFC. Notably, clusterin has a protective effect on cardiomyocytes after acute MI in vivo and is an important mediator of TGFß-induced. Clusterin addition to the pericardial sac determined an increase in epicardial cells expressing the EMT marker α-SMA and, interestingly, an increase in the number of epicardial cells ckit(+)/α-SMA(+), 7days following MI. Importantly, clusterin treatment enhanced arteriolar length density and lowered apoptotic rates in the peri-infarct area. Hemodynamic studies demonstrated an improvement in cardiac function in clusterin-treated compared to untreated infarcted hearts. CONCLUSIONS: Exosomes are present and detectable in the PFs. Clusterin was identified in PFMI-exosomes and might account for an improvement in myocardial performance following MI through a framework including EMT-mediated epicardial activation, arteriogenesis and reduced cardiomyocyte apoptosis.

Aortic valve replacement following coronary artery bypass grafting using bilateral internal mammary arteries.

Aortic valve replacement in patients with a patent internal mammary artery grafts poses two main challenges: Sternal reentry and myocardial protection. Beating heart procedures have been well described in coronary and valve surgery. Herein, we describe a simple reproducible technique of aortic valve replacement that circumvents the main issues highlighted above.

Spinal infarction following coronary artery bypass grafting.

Spinal infarction is an extremely rare complication of coronary artery bypass grafting (CABG), almost invariably associated with use of the intra-aortic balloon pump (IABP). We present the case of a 63-year-old lady who developed paraplegia, secondary to spinal infarction, following CABG in whom the IABP was not used and no other predisposing factors were present.

Aortic pseudoaneurysm complicating sternal wound infection following CABG.

Pseudoaneurysm of the ascending aorta following coronary artery bypass grafting is a rare complication. In this report we present two such cases. We were successful in repairing the false aneurysm and sternal dehiscence in one case. The clinical features, diagnosis and surgical management are discussed.

Pneumomediastinum during spontaneous vaginal delivery.

We report two rare cases of spontaneous pneumomediastinum that presented shortly after childbirth and resolved without treatment. Spontaneous pneumomediastinum has been described in a wide range of seemingly unrelated but recurrent clinical scenarios. We highlight their common etiologic factors and provide the anatomic and physiologic bases for the radiologic signs that are common in all these conditions.

Heartport endoclamp for complex cardiac repairs with total circulatory arrest.

A method of performing redo cardiac operations using port-access technology and total circulatory arrest is described. The technique was useful in 2 cases requiring re-intervention within 4 months of the primary procedure. The indications were repair of an infected ventricular aneurysm and recurrence of a postinfarction ventricular septal defect. Dense mediastinal adhesions were avoided by approaching the site of pathology directly via a left anterior thoracotomy.