Raffaele Barbato

The role of extracellular matrix in age-related conduction disorders: a forgotten player?

Cardiovascular aging is a physiological process gradually leading to structural degeneration and functional loss of all the cardiac and vascular components. Conduction system is also deeply influenced by the aging process with relevant reflexes in the clinical side. Age-related arrhythmias carry significant morbidity and mortality and represent a clinical and economical burden. An important and unjustly unrecognized actor in the pathophysiology of aging is represented by the extracellular matrix (ECM) that not only structurally supports the heart determining its mechanical and functional properties, but also sends a biological signaling regulating cellular function and maintaining tissue homeostasis. At the biophysical level, cardiac ECM exhibits a peculiar degree of anisotropy, which is among the main determinants of the conductive properties of the specialized electrical conduction system. Age-associated alterations of cardiac ECM are therefore able to profoundly affect the function of the conduction system with striking impact on the patient clinical conditions. This review will focus on the ECM changes that occur during aging in the heart conduction system and on their translation to the clinical scenario. Potential diagnostic and therapeutical perspectives arising from the knowledge on ECM age-associated alterations are further discussed.

The fate of large-diameter Dacron® vascular grafts in surgical practice: Are we really satisfied?

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Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts

BACKGROUND Advanced glycation endproducts (AGEs) and its receptors (RAGEs) are heterogeneous signaling proteins associated to diabetes and responsible of endothelial alterations leading to atherosclerosis progression and graft failure. The aim of this study was to investigate the role of statin in reducing AGEs related endothelial damage. METHODS Endothelial cell(EC) obtained from leftovers of saphenous vein grafts of non-diabetic patients were incubated with AGEs (2 and 20 μM) and subsequently treated with Simvastatin. Neutrophils (PNM) adherence, ROS production and RAGE and peroxisome proliferator-activated receptors-gamma (PPAR-γ) expression were analyzed. As clinical validation of the in vitro findings, ECs of diabetic patients in optimized glycaemic control administered with a 3 weeks Simvastatin regimen were similarly processed. RESULTS Simvastatin blunted the rise in PMN adhesion and ROS generation following stimulation of saphenous vein EC culture with AGEs in vitro. This effect was time dependent and was associated to an increase in PPAR-γ induction paralleled by a decrease in RAGEs expression. Parallely, data from diabetic patients administered with Simvastatin showed a similar significant reduction in PNM adhesion and ROS generation. Simvastatin treatment significantly decreased RAGEs expression in ECs from diabetic patients and determined a slight increase in PPAR-γ expression but the latter failed to reach statistical significance. Interference in the function of these two crucial pathways might be at the root of the statin antinflammatory and antithrombotic effect in the context of AGEs-associated damage. CONCLUSIONS Despite the recently raised warning on the use of statins in the diabetic population, this study elucidates their cornerstone position in endothelial homeostasis of saphenous grafts in patients with controlled diabetes.

Pressure ulcers in cardiac surgery: Few clinical studies, difficult risk assessment, and profound clinical implications

Pressure ulcers (PUs) are a common complication after cardiac surgery, with almost one third of patients suffering from PUs during hospitalisation. Because of the burden that PUs exert on both the patients and the health care system, prevention is of utmost importance. The first step in successful prevention, however, includes the identification of the main features that render patients prone to PU development. Cardiac surgery population is not adequately addressed in current clinical trials and studies. Few studies focused specifically on cardiac surgery patients, but the majority included cardiac surgery patients within a heterogeneous population of acute or critical care patients. Therefore, additional research is warranted to understand the unique risk profile of patients undergoing cardiac surgery. Intraoperative risk factors that affect tissue tolerance have not been thoroughly investigated but are likely to play an important role, which might explain the epidemiology of a PU. Further research is also needed to better comprehend the risk of PUs among cardiac surgery patients and to design effective and tailored preventative measures with the help of newer tools for risk assessment.

Levosimendan in Cardiac Surgery: Is it all Gold that Glitters?

Patients undergoing cardiac surgery are becoming older and with greater comorbidities, carrying an increased risk for perioperative complications which result in higher mortality and higher costs for the health care service [1]. One of the most demanding complications, in terms of morbidity and costs, is the low cardiac output syndrome (LCOS), which occurs in 10-15% of patients undergoing cardiac surgery with cardiopulmonary bypass [2,3]. LCOS is generally more common among patients with impaired left ventricular function, and is managed with inotropic agents and, eventually, mechanical support such as intra-aortic balloon pump, extracorporeal membrane oxygenator or ventricular assist devices. Although recent advances in pharmacologic and mechanical treatments, short-term mortality risk for patients with LCOS remains up to 15 times higher compared to an uneventful post-operative course [1]. Most of the available inotropic agents have detrimental side effect or have a poor safety profile, thus exposing the patient to treatment-related risks and complications. The prevention and the effective treatment of LCOS is one of the pivotal requirement to improve outcomes in cardiac surgery.