Front Cardiovasc Med
June 2023
Cardioplegic cardioprotection strategies used during paediatric open-heart surgery remain suboptimal. Sildenafil, a phosphodiesterase 5 (PDE-5) inhibitor, has been shown to be cardioprotective against ischemia/reperfusion injury in a variety of experimental models and this study therefore tested the efficacy of supplementation of cardioplegia with sildenafil in a piglet model of cardiopulmonary bypass and arrest, using both cold and warm cardioplegia protocols. Piglets were anaesthetized and placed on coronary pulmonary bypass (CPB), the aorta cross-clamped and the hearts arrested for 60 min with cardioplegia with or without sildenafil (10 nM).
View Article and Find Full Text PDFIntroduction: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is known to be responsible for ischaemia and reperfusion organ injury. In a previous study, ProMPT, in patients undergoing coronary artery bypass or aortic valve surgery we demonstrated improved cardiac protection when supplementing the cardioplegia solution with propofol (6 mcg/ml). The aim of the ProMPT2 study is to determine whether higher levels of propofol added to the cardioplegia could result in increased cardiac protection.
View Article and Find Full Text PDFFront Cardiovasc Med
July 2022
Introduction: Changes in cardiac metabolites in adult patients undergoing open-heart surgery using ischemic cardioplegic arrest have largely been reported for non-ventricular tissue or diseased left ventricular tissue, with few studies attempting to assess such changes in both ventricular chambers. It is also unknown whether such changes are altered in different pathologies or linked to the degree of reperfusion injury and inflammatory response. The aim of the present work was to address these issues by monitoring myocardial metabolites in both ventricles and to establish whether these changes are linked to reperfusion injury and inflammatory/stress response in patients undergoing surgery using cold blood cardioplegia for either coronary artery bypass graft (CABG, = 25) or aortic valve replacement (AVR, = 16).
View Article and Find Full Text PDFBackground: The role of cardiac autophagy during ischemia and reperfusion (I/R) remains controversial. Furthermore, whether this cell death during I/R is also interconnected with other cell damaging event, such as necroptosis, is insufficiently known. Thus, the aim of this study was to investigate possible links between autophagy and necroptosis in the hearts under conditions of acute I/R injury.
View Article and Find Full Text PDFOur earlier work has shown inter‑disease and intra‑disease differences in the cardiac proteome between right (RV) and left (LV) ventricles of patients with aortic valve stenosis (AVS) or coronary artery disease (CAD). Whether disease remodeling also affects acute changes occuring in the proteome during surgical intervention is unknown. This study investigated the effects of cardioplegic arrest on cardiac proteins/phosphoproteins in LV and RV of CAD (n=6) and AVS (n=6) patients undergoing cardiac surgery.
View Article and Find Full Text PDFBackground: Mature cardiomyocytes are unable to proliferate, preventing the injured adult heart from repairing itself. Studies in rodents have suggested that the extracellular matrix protein agrin promotes cardiomyocyte proliferation in the developing heart and that agrin expression is downregulated shortly after birth, resulting in the cessation of proliferation. Agrin based therapies have proven successful at inducing repair in animal models of cardiac injury, however whether similar pathways exist in the human heart is unknown.
View Article and Find Full Text PDFAims/hypothesis: Diabetic cardiomyopathy (DCM) is a serious and under-recognised complication of diabetes. The first sign is diastolic dysfunction, which progresses to heart failure. The pathophysiology of DCM is incompletely understood but microcirculatory changes are important.
View Article and Find Full Text PDFExtensive research work has been carried out to define the exact significance and contribution of regulated necrosis-like cell death program, such as necroptosis to cardiac ischemic injury. This cell damaging process plays a critical role in the pathomechanisms of myocardial infarction (MI) and post-infarction heart failure (HF). Accordingly, it has been documented that the modulation of key molecules of the canonical signaling pathway of necroptosis, involving receptor-interacting protein kinases (RIP1 and RIP3) as well as mixed lineage kinase domain-like pseudokinase (MLKL), elicit cardioprotective effects.
View Article and Find Full Text PDFCoronary artery occlusion (45 min) and reperfusion (2 h) was performed in rats anesthetized with α-chloralose. Opioid receptor agonists were administered intravenously 5 min before reperfusion, while opioid receptor antagonists were administered 10 min before reperfusion. The non-selective opioid δ-receptor agonist DADLE at a dose of 0.
View Article and Find Full Text PDFThe cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischaemia/reperfusion of isolated perfused heart. We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). 8-Br (10 μM) was administered to Langendorff-perfused rat hearts for 5 min either before or at the end of 30 min regional ischaemia.
View Article and Find Full Text PDFHuman saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV.
View Article and Find Full Text PDFNeonates with coarctation of the aorta (CoA) combined with a bicuspid aortic valve (BAV) show significant structural differences compared to neonatal CoA patients with a normal tricuspid aortic valve (TAV). These effects are likely to change over time in response to growth. This study investigated proteomic differences between coarcted aortic tissue of BAV and TAV patients in children older than one month.
View Article and Find Full Text PDFThe mechanisms underlying the protective effects of remote ischemic preconditioning (RIPC) are not presently clear. Recent studies in experimental models suggest the involvement of the autonomic nervous system (ANS) in cardioprotection. The aim of this study was to investigate the changes in ANS in healthy young volunteers divided into RIPC (n = 22) or SHAM (n = 18) groups.
View Article and Find Full Text PDFCoarctation of the aorta is a form of left ventricular outflow tract obstruction in paediatric patients that can be presented with either bicuspid (BAV) or normal tricuspid (TAV) aortic valve. The congenital BAV is associated with hemodynamic changes and can therefore trigger different molecular remodelling in the coarctation area. This study investigated the proteomic and phosphoproteomic changes associated with BAV for the first time in neonatal coarctation patients.
View Article and Find Full Text PDFObjectives: This trial was designed and patients were recruited at a time when the benefits of remote ischaemic preconditioning during open-heart surgery were still controversial. We focused on a homogeneous patient population undergoing either isolated aortic valve replacement or coronary artery bypass grafting (CABG) surgery by investigating cardiac injury, metabolic stress and inflammatory response.
Methods: A 2-centre randomized controlled trial recruited a total of 124 patients between February 2013 and April 2015.
Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff-perfused hearts from adult and immature (60 and 14 days old) male Wistar rats were exposed to 30 min ischemia and 120 min reperfusion, with or without prior perfusion with 5 nM Iso for 3 min followed by 30 μM Aden for 5 min.
View Article and Find Full Text PDFObjectives: Combined coronary artery bypass grafting and valve surgery requires a prolonged period of cardioplegic arrest (CA) predisposing to myocardial injury and postoperative cardiac-specific complications. The aim of this trial was to reduce the CA time in patients undergoing combined coronary artery bypass grafting and valve surgery and assess if this was associated with less myocardial injury and related complications.
Methods: Participants were randomized to (i) coronary artery bypass grafting performed on the beating heart with cardiopulmonary bypass support followed by CA for the valve procedure (hybrid) or (ii) both procedures under CA (conventional).
Cardioprotective efficacy of remote ischemic preconditioning (RIPC) remains controversial. Experimental studies investigating RIPC have largely monitored cardiovascular changes during index ischemia and reperfusion with little work investigating changes during RIPC application. This work aims to identify cardiovascular changes associated with autonomic nervous system (ANS) activity during RIPC and prior to index ischemia.
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