A Minimally-Invasive Swine Model of Chronic Kidney Disease-Associated Heart Failure.

Background: Chronic kidney disease (CKD) is on the rise, and over 50% of patients die from cardiac causes. Patients develop heart failure due to unelucidated reno-cardiac interactions, termed type 4 cardiorenal syndrome (CRS4). The aim of this study is to establish and characterize a reliable model of CRS4 in swine with marked cardiac diastolic dysfunction.

AAV delivery strategy with mechanical support for safe and efficacious cardiac gene transfer in swine.

Adeno-associated virus-based gene therapy is a promising avenue in heart failure treatment, but has shown limited cardiac virus uptake in humans, requiring new approaches for clinical translation. Using a Yorkshire swine ischemic heart failure model, we demonstrate significant improvement in gene uptake with temporary coronary occlusions assisted by mechanical circulatory support. We first show that mechanical support during coronary artery occlusions prevents hemodynamic deterioration (n = 5 female).

Inhibition of endothelial-to-mesenchymal transition in a large animal preclinical arteriovenous fistula model leads to improved remodelling and reduced stenosis.

Aims: Vein grafts are used for many indications, including bypass graft surgery and arteriovenous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia, and adverse remodelling. Recently, endothelial-to-mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts.

Swine Model of Coronary Artery Dissection.

Coronary artery dissection (CAD) is the intimal tearing of the coronary arterial wall and can be iatrogenic, spontaneous, or traumatic in origin. CAD is a rare but challenging condition that can cause significant hemodynamic compromise. Management strategies for CAD, such as the use of mechanical circulatory support devices, are available in the clinical setting.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear.

Negative Impact of Acute Reloading after Mechanical Left Ventricular Unloading.

Mechanical LV unloading for acute myocardial infarction (MI) is a promising supportive therapy to reperfusion. However, no data is available on exit strategy. We evaluated hemodynamic and cellular effects of reloading after Impella-mediated LV unloading in Yorkshire pigs.

Progress in Clinical Gene Therapy for Cardiac Disorders.

Despite significant advances in novel treatments and approaches, cardiovascular disease remains the leading cause of death globally. Gene therapy is a promising option for many diseases, including cardiovascular diseases. In the last 30 years, gene therapy has slowly proceeded towards clinical translation and recently reached US Food and Drug Administration approval for several diseases such as Leber congenital amaurosis and spinal muscular atrophy, among others.

Device-Based Approaches Targeting Cardioprotection in Myocardial Infarction: The Expanding Armamentarium of Innovative Strategies.

Coronary reperfusion therapy has played a pivotal role for reducing mortality and heart failure after acute myocardial infarction. Although several adjunctive approaches have been studied for reducing infarct size further, both ischemia-reperfusion injury and microvascular obstruction are still major contributors to both early and late clinical events after acute myocardial infarction. The progress in the field of cardioprotection has found several promising proof-of-concept preclinical studies.

Assessing the Effect of Cardiac Gene Therapy Using Catheter-Based Pressure-Volume Measurement in Large Animals.

Gene therapy for heart failure targets various pathways that modulate cardiac function. Its detailed evaluation is crucial for proving the efficacy of cardiac gene therapies. Parameters that can be obtained by noninvasive approaches are generally influenced by loading conditions of the heart.

Left Ventricular Pressure Volume Assessment Using Carotid Artery Access in the Rat.

Left ventricular (LV) catheterization with either a pressure catheter or pressure-volume catheter provides a means to measure cardiac function, an important endpoint in many studies including cardiac gene therapy. While the catheter can be inserted directly into the heart using a surgical approach, utilizing the carotid artery for access has the advantage of being a closed-chest procedure. This negates the need for intubation, prevents myocardial trauma, and preserves normal intrathoracic pressure, providing more accurate assessments of cardiac physiology parameters.

Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques.

Percutaneous antegrade coronary injection is among the least invasive cardiac selective gene delivery methods. However, the transduction efficiency of a simple bolus antegrade injection is quite low. In order to improve transduction efficiency in antegrade intracoronary delivery, several additional approaches have been proposed.

Impact of ischemia on left atrial remodeling and dysfunction in swine models of mitral regurgitation.

Left atrial (LA) dysfunction is one of the predictive factors of worse outcomes after mitral valve surgery for mitral regurgitation (MR). We aimed to investigate the effect of MR etiology on progression of LA remodeling in swine MR models. MR was induced in 14 Yorkshire pigs using catheter-based procedures.

Nicotinic acetylcholine receptor-mediated protection of the rat heart exposed to ischemia reperfusion.

Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically alpha-7 subtype (α7nAChR) in the myocardium remains unknown which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications.