Publications by authors named "Sellke F"

Article Synopsis
  • Alzheimer's disease (AD) is characterized by various pathological features including amyloid-β deposition and tau hyperphosphorylation, with cerebral microvascular dysfunction likely playing a role in its progression.
  • Researchers investigated the microvascular responses and potassium channel activity in an AD mouse model induced by streptozotocin (STZ), using behavioral tests and cellular assays.
  • The study found that STZ-AD mice showed poorer performance on behavioral tests and had impaired microvascular responses, which were further deteriorated by exposure to soluble Aβ, indicating a potential link between microvascular dysfunction and AD pathology.
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Background: We sought to identify predictors of acute renal failure (ARF) following acute type A aortic dissection (ATAAD) and its implications on postoperative outcomes.

Methods: ATAAD cases were identified from The Society of Thoracic Surgeons - Adult Cardiac Surgery Database (2017-2022). Cases with chronic dissection, prior aortic repair, primary endovascular repair, preoperative extracorporeal membrane oxygenation, preoperative renal failure, and operative room deaths were excluded.

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The promise of injection of extracellular matrix (ECM) from animal hearts as a treatment of myocardial ischemia has been limited by immune reactions and harsh ECM-damaging extraction procedures. We developed a novel method to produce lab-grown human three-dimensional (3-D) acellular ECM particles from human mesenchymal stem cells (MSCs) to mitigate product variability, immunogenicity, and preserve ECM architecture. We hypothesized that intramyocardial injection (I/M) of this novel ECM (dia ∼ 200 microns) would improve cardiac function in a postmyocardial infarction (MI) murine model.

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Background: Coronary artery disease is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy and up to one-thirds with debilitating angina amenable neither to procedures, nor to current pharmacological options. Semaglutide (SEM), a GLP-1 (glucagon-like peptide 1) agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk.

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Background: Cardioplegic ischemia/reperfusion (I/R) injury poses substantial challenges during postoperative recovery, with diabetic patients particularly susceptible to adverse events. Using a model entailing the subjection of human coronary artery endothelial cells (HCAECs) to simulated cardioplegic I/R, we investigated the potential of protein kinase c β (PKC-β) inhibition to augment cellular survival in this context.

Study Design: HCAECs were isolated from harvested coronary arteries of diabetic (D) and nondiabetic (C) patients (N = 4 per group).

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Background: Emerging data suggest women have worse outcomes than men following cardioplegia and cardiopulmonary bypass (CP/CPB). Altered coronary microvascular function affecting myocardial perfusion may contribute, but human translational studies are lacking.

Methods: Viable coronary microvessels (<200 μ m) were dissected from human atrial samples collected before and after CP/CPB from a subset of 108 patients enrolled.

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Background: Transfemoral (TF) access is the preferred approach for transcatheter aortic valve replacement (TAVR). Limited data exist regarding the outcomes of intravascular lithotripsy (IVL)-assisted TF TAVR in patients with peripheral artery disease.

Objectives: This study sought to examine contemporary characteristics, trends, and outcomes of IVL TAVR in the United States.

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Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown efficacy in the context of heart failure but have not been well-studied in ischemic heart disease. We employed a large animal model of chronic coronary artery disease and metabolic syndrome (MS) to investigate the hemodynamic and metabolic consequences of SGLT2i administration.

Methods: Thirty-eight Yorkshire swine were divided into two groups, with half (n = 21) receiving a high fat diet to induce MS, and the other half fed a standard diet (n = 17).

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Background: Lung cancer remains the greatest cause of cancer-related death, and multiple large studies have identified persistent racial disparities in lung cancer outcomes. In this study, we used public recording of lung cancer data on clinicaltrials.gov to sample age, gender, racial, and ethnic characteristics of participants in lung cancer clinical trials.

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Objective: Coronary artery disease remains a leading cause of morbidity and mortality worldwide. Patients with advanced coronary artery disease who are not eligible for endovascular or surgical revascularization have limited options. Extracellular vesicles have shown potential to improve myocardial function in preclinical models.

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Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed.

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Objective: Coronary artery disease (CAD) is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy, and up to 1/3 with debilitating angina amenable neither to procedures, nor to current pharmacologic options. Semaglutide, a glucagon-like peptide 1 agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk.

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Aim: Recent studies demonstrate that sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i), two classes of antidiabetic drugs, are cardioprotective. However, the mechanisms of these benefits and their comparative efficacy remain unclear. We aimed to compare the effects of these antidiabetic agents on cardiac function, perfusion, and microvascular density using a swine model of chronic myocardial ischemia.

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Although both clinical data and animal models suggest cardiovascular benefits following administration of Dipeptidyl Peptidase 4 (DPP-4) inhibitors, the underlying mechanisms remain unclear. We therefore sought to evaluate the effect of the DPP-4 inhibitor sitagliptin on myocardial fibrosis, and insulin signaling in chronic myocardial ischemia using a swine model. An ameroid constrictor placement on the left coronary circumflex artery of thirteen Yorkshire swine to model chronic myocardial ischemia.

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Objective: To test the efficacy of metformin (MET) during the induction of coronary ischemia on myocardial performance in a large animal model of coronary artery disease (CAD) and metabolic syndrome (MS), with or without concomitant extracellular vesicular (EV) therapy.

Background: Although surgical and endovascular revascularization are durably efficacious for many patients with CAD, up to one-third are poor candidates for standard therapies. For these patients, many of whom have comorbid MS, adjunctive strategies are needed.

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Cardiopulmonary bypass (CPB) initiates an intense inflammatory response due to various factors: conversion from pulsatile to laminar flow, cold cardioplegia, surgical trauma, endotoxemia, ischemia-reperfusion injury, oxidative stress, hypothermia, and contact activation of cells by the extracorporeal circuit. Redundant and overlapping inflammatory cascades amplify the initial response to produce a systemic inflammatory response, heightened by coincident activation of coagulation and fibrinolytic pathways. When unchecked, this inflammatory response can become maladaptive and lead to serious postoperative complications.

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Article Synopsis
  • Heart failure (HF) is a major reason for patients being readmitted to the hospital after cardiac surgery, but the specific risk factors are not well understood.
  • This study used data from the National Readmissions Database to identify risk factors for 30-day HF readmissions in patients who underwent various types of cardiac surgeries.
  • Key risk factors found included older age, female gender, prolonged hospital stays, and certain pre-existing health conditions, with prior coronary artery bypass grafting (CABG) providing some protection against readmission.
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Introduction: Sodium-glucose cotransporter-2 inhibitors are antidiabetic medications that have been shown to decrease cardiovascular events and heart failure-related mortality in clinical studies. We attempt to examine the complex interplay between metabolic syndrome and the sodium-glucose cotransporter-2 inhibitor canagliflozin (CAN) in a clinically relevant model of chronic myocardial ischemia.

Methods: Twenty-one Yorkshire swine were fed a high-fat diet starting at 6 weeks of age to induce metabolic syndrome.

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Since the invention of cardiopulmonary bypass, cardioprotective strategies have been investigated to mitigate ischemic injury to the heart during aortic cross-clamping and reperfusion injury with cross-clamp release. With advances in cardiac surgical and percutaneous techniques and post-operative management strategies including mechanical circulatory support, cardiac surgeons are able to operate on more complex patients. Therefore, there is a growing need for improved cardioprotective strategies to optimize outcomes in these patients.

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Background: We previously found that cardioplegic arrest and cardiopulmonary bypass are associated with altered coronary arteriolar response to serotonin in patients undergoing cardiac surgery. In this study, we investigated the effects of hypertension on coronary microvascular vasomotor tone in response to serotonin and alterations in serotonin receptor protein expression in the setting of cardioplegic arrest and cardiopulmonary bypass.

Methods: Coronary arterioles were dissected from harvested pre- and post-cardioplegic arrest and cardiopulmonary bypass right atrial tissue samples of patients undergoing cardiac surgery with normotension, well-controlled hypertension, and uncontrolled hypertension.

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Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and are still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain.

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Gastrointestinal complications after cardiac surgery are relatively rare entities but carry a high mortality. We identified over 70 articles written since 2010 using the PubMed database. We included 40 in our review.

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Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to be cardioprotective independent of glucose control, but the mechanisms of these benefits are unclear. We previously demonstrated improved cardiac function and decreased fibrosis in a swine model of chronic myocardial ischemia. The goal of this study is to use high-sensitivity proteomic analyses to characterize specific molecular pathways affected by SGLT-2 inhibitor canagliflozin (CAN) therapy in a swine model of chronic myocardial ischemia.

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Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. In particular, patients who suffer from ischemic heart disease (IHD) that is not amenable to surgical or percutaneous revascularization techniques have limited treatment options. Furthermore, after revascularization is successfully implemented, there are a number of pathophysiological changes to the myocardium, including but not limited to ischemia-reperfusion injury, necrosis, altered inflammation, tissue remodeling, and dyskinetic wall motion.

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