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Vascular smooth muscle cells (VSMCs) show a remarkable phenotypic plasticity, allowing acquisition of contractile or synthetic states, but critical information is missing about the physiologic signals, promoting formation, and maintenance of contractile VSMCs in vivo. BMP9 and BMP10 (bone morphogenetic protein) are known to regulate endothelial quiescence after secretion from the liver and right atrium, whereas a direct role in the regulation of VSMCs was not investigated. We studied the role of BMP9 and BMP10 for controlling formation of contractile VSMCs.

We generated several cell type-specific loss- and gain-of-function transgenic mouse models to investigate the physiologic role of BMP9, BMP10, ALK1 (activin receptor-like kinase 1), and SMAD7 in vivo. BIX 01294 manufacturer Morphometric assessments, expression analysis, blood pressure measurements, and single molecule fluorescence in situ hybridization were performed together with analysis of isolated pulmonary VSMCs to unravel phenotypic and transcriptomic changes in responed-specific, heterogeneous expression of BMP type 1 receptors, explaining phenotypic differences in different

mutant vessel beds.

Our study demonstrates that BMP9 and BMP10 act directly on VSMCs for induction and maintenance of their contractile state. The effects of BMP9/10 in VSMCs are mediated by different combinations of BMP type 1 receptors in a vessel bed-specific manner, offering new opportunities to manipulate blood pressure in the pulmonary circulation.

Our study demonstrates that BMP9 and BMP10 act directly on VSMCs for induction and maintenance of their contractile state. The effects of BMP9/10 in VSMCs are mediated by different combinations of BMP type 1 receptors in a vessel bed-specific manner, offering new opportunities to manipulate blood pressure in the pulmonary circulation.Ticagrelor is a potent reversible P2Y12 inhibitor with proven superiority over clopidogrel. Ticagrelor increases the tissue concentration of adenosine, thereby leading to bradyarrhythmia. This complication is reported to occur very early after initiating the drug. A randomized controlled trial reported that ticagrelor-induced pauses have an early onset without much clinical impact. However, our patient developed ticagrelor-induced hemodynamically significant sinus arrest 10 months after coronary artery stenting, which improved after stopping the drug. Ticagrelor should be considered as one of the uncommon reasons for late-onset sinus pause or bradyarrhythmia.

Concerns have been raised regarding whether skeletonization of the internal thoracic artery could damage the graft and thereby reduces its patency. The objective of this study was to compare patency rates at mid- and long-term follow-up between pedicled and skeletonized left internal thoracic artery grafts.

This randomized controlled trial included 109 patients undergoing coronary artery bypass surgery. The patients were assigned to receive either one pedicled or one skeletonized left internal thoracic artery graft to the left anterior descending artery. Follow-up was performed at 3 years with conventional angiography, and at 8 years with computed tomography angiography. Differences between patency rates were analyzed with Fisher’s exact test and a generalized linear model.

The patency rates for pedicled and skeletonized left internal thoracic artery grafts were 46/48 (95.8%) versus 47/52 (90.4%),

 = 0.44 at 3 years, and 40/43 (93.0%) versus 37/41 (90.2%),

 = 0.71 at 8 years, respectively. The difference in patency rates for pedicled and skeletonized grafts was 5.4% (95% confidence interval -4.2-14.5) at 3 years and 2.8% (95% confidence interval -9.9-14.1) at 8 years. All failed grafts, except for one with a localized stenosis, were anastomosed to native coronary arteries with a stenosis less than 70%. Three patients suffered sternal wound infections (two in the pedicled group, one in the skeletonized group).

The skeletonization technique can be used without jeopardizing the patency of the left internal thoracic artery. The most important factor in graft failure was target artery stenosis below 70%.

The skeletonization technique can be used without jeopardizing the patency of the left internal thoracic artery. The most important factor in graft failure was target artery stenosis below 70%.

Valved homografts are commonly used for right ventricular outflow tract reconstruction. However, despite good early results, they lack durability. This study was designed to compare single-center results of implantation of 3 types of right ventricular outflow tract conduit, in terms of patient survival, graft failure, reoperation, and risk factors for reoperation.

One hundred and forty-three pediatric patients who underwent right ventricular outflow tract conduit implantation between January 2006 and December 2018 were reviewed. We stratified conduits by aortic, pulmonic homograft, and Contegra; 74 aortic homografts, 61 pulmonic homografts, and 8 Contegra conduits were implanted. Median age at implantation was 3 years. The primary diagnosis was truncus arteriosus in 41.3%. We analyzed the role of sex, age, diagnosis, and graft size. Endpoints included freedom from graft failure, freedom from reoperation, and survival.

The survival rate was 83.2% at 10 years. Freedom from graft failure at 2, 5, and 10 years was 100%, 97.9%, and 63.4%, respectively. Freedom from reoperation was 85.8% for pulmonic homografts and 74.9% for aortic homografts at 10 years, and 100% for Contegra at 6 years. Multivariable analysis identified conduit diameter <18 mm as a risk factor for reoperation (hazard ratio 3.16, 95% confidence interval 1.38-7.23,

 = 0.007).

Homograft valves used for right ventricular outflow tract reconstruction provided excellent long-term durability and late survival. The only factor that adversely affected graft longevity was small graft size (diameter <18 mm). Reoperation for conduit failure was not significantly different among the groups.

Homograft valves used for right ventricular outflow tract reconstruction provided excellent long-term durability and late survival. The only factor that adversely affected graft longevity was small graft size (diameter less then 18 mm). Reoperation for conduit failure was not significantly different among the groups.