Background: Endothelial injury occurring during cardiopulmonary bypass is a major contributing factor in the development of organ dysfunction, which leads to many of the postoperative complications occurring during cardiac surgery. Objective: This narrative review aims to summarize the main mechanisms of cardiopulmonary bypass - related disease, evaluating the unfavorable events leading to tissue injury, with a description of current pharmacologic and non-pharmacologic mechanisms to reduce CPB-related injury. Methods: A Medline/Pubmed/Scopus search was conducted using clinical queries with the key terms "cardiac surgery", “cardiopulmonary bypass”, "inflammation" and “endothelial injury”, and related MeSH terms, until July 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the same key terms from https://patents.google.com/, www.uspto.gov, and www.freepatentsonline.com. Results: In this review, we discuss the current knowledge of the mechanisms of vascular endothelial cell injury, the acute inflammatory response, and the regulatory factors that control the extent of vascular injury during extracorporeal circulation, summarizing the main target of anti-inflammatory pharmacologic and non-pharmacologic strategies. Conclusion: Inflammatory response and endothelial dysfunction following cardiopulmonary bypass are the prices to pay for the benefits offered during cardiac surgery procedures. Counteracting the detrimental effect of extracorporeal circulation appears to be crucial to improve clinical outcomes in pediatric and adult cardiac surgery. The intrinsic complexity and the tight interplay of the factors involved might require a holistic approach against inflammation and endothelial response.

Despite the dramatic improvements of revascularization therapies occurring in the past decades, a relevant percentage of patients treated with percutaneous coronary intervention (PCI) still develops stent failure due to neo-atherosclerosis (NA). This histopathological phenomenon following stent implantation represents the substrate for late in-stent restenosis (ISR) and late stent thrombosis (ST), with a significant impact on patient’s long-term clinical outcomes. This appears even more remarkable in the setting of drug-eluting stent implantation, where the substantial delay in vascular healing because of the released anti-proliferative agents might increase the occurrence of this complication. Since the underlying pathophysiological mechanisms of NA diverge from native atherosclerosis and early ISR, intra-coronary imaging techniques are crucial for its early detection, providing a proper in vivo assessment of both neo-intimal plaque composition and peri-strut structures. Furthermore, different strategies for NA prevention and treatment have been proposed, including tailored pharmacological therapies as well as specific invasive tools. Considering the increasing population undergoing PCI with drug-eluting stents (DES), this review aims to provide an updated overview of the most recent evidence regarding NA, discussing pathophysiology, contemporary intravascular imaging techniques, and well-established and experimental invasive and pharmacological treatment strategies.

Purpose. Statins are a class of drugs widely used in clinical practice for their lipid‐lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin‐platelet interaction in the cardiologic scenario and building the basis for future in‐depth studies. Methods. We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020. Results. Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX‐1), recruitment and adhesion (LOX‐1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel. Conclusion. There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in‐depth studies.

A previously developed poly-l-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling. These findings were coupled with a reduction in end-systolic and end-diastolic volumes, indicating a preventive effect of the scaffold on ventricular dilation, and an improvement in cardiac performance.