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Background: Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca2+) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca2+ oscillations and the Ca2+ toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes.Methods and Results: ACM C-MSC show enhanced spontaneous Ca2+ oscillations and concomitant increased Ca2+/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca2+ Entry (SOCE), which leads to enhanced Ca2+ release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca2+ handling machinery or CaMKII activity, we demonstrated a causative link between Ca2+ oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca2+ signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca2+ oscillations and fibro-adipogenic differentiation by selectively targeting SOCE.Conclusions: Altogether, our results extend the knowledge of Ca2+ dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM. [ABSTRACT FROM AUTHOR]

Background: The aim of this prospective study is to evaluate the role in the onset of surgical site infections of bilateral internal thoracic arteries harvesting in patients with decompensated preoperative glycemia. Methods: 81 consecutive patients with uncontrolled diabetes mellitus underwent elective CABG harvesting single or double internal thoracic arteries. Single left ITA was harvested in 41 patients (Group 1, 50.6%), BITAs were harvested in 40 (Group 2, 49.4%). The major clinical end points analyzed in this study were infection rate, type of infection, duration of infection, infection relapse rate and total hospital length of stay. Results: Five patients developed sternal SSI in the perioperative period, 2 in group 1 and 3 in group 2 without significant difference. All sternal SSIs were superficial with no sternal dehiscence. The development of infection from the time of surgery took 18.5 ± 2.1 and 7.3 ± 3.0 days for Groups 1 and 2 respectively. The infections were treated with wound irrigation and debridement, and with VAC therapy as well as with antibiotics. The VAC system was removed after a mean of 12.8 ± 5.1 days, when sterilization was achieved. The overall survival estimate at 1 year was 98.7%. Only BMI was a significant predictor of SSI using multivariate stepwise logistic regression analysis (Odds Ratio: 1.34; 95%Conficdence Interval: 1.02-1.83; p value: 0.04). In the model, the use of BITA was not an independent predictor of SSI. Conclusion: CABG with bilateral pedicled ITAs grafting could be performed safely even in diabetics with poor preoperative glycaemic control. [ABSTRACT FROM AUTHOR]

Background: This study was undertaken to compare the in vitro effects of 17β-estradiol on human epicardial coronary arteries, resistance coronary arteries and on arterial vessels usually employed as grafts in surgical myocardial revascularization. Methods: Coronary artery rings (descending coronary artery, right coronary artery, circumflex coronary artery, first septal branch) and arterial graft rings (internal thoracic artery, gastroepiploic artery) obtained from human heart donors with heart not suitable to cardiac transplantation were connected to force transducer for isometric force recording. Precontracted specimens with and without endothelium were exposed to increasing concentration of 17β-estradiol (3-30-300-3000 nmol/l) and to vehicle (0.1% v/v ethanol). We also evaluated the effects of 17β-estradiol on vessels before and 20 minutes after exposure to L-monomethyl-arginine and indomethacin. Results: 17β-estradiol induced a significant relaxation in all precontracted vessels (mean maximum effect: 78,6% ± 8,5). This effect was not different among the different rings and was not related to the presence of endothelium. N-monomethyl-L-arginine and indomethacin did not modify 17β-estradiol relaxant effect. Conclusion: The vasodilator action of the 17β-estradiol is similar on coronary arteries, resistance coronary arteries and arterial vessels usually employed as grafts in myocardial revascularization. [ABSTRACT FROM AUTHOR]