A Comparative Investigation of the Pulmonary Vasodilating Effects of Inhaled NO Gas Therapy and Inhalation of a New Drug Formulation Containing a NO Donor Metabolite (SIN-1A).

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension.

In a rat model of bypass DuraGraft ameliorates endothelial dysfunction of arterial grafts.

Coronary artery bypass surgery can result in endothelial dysfunction due to ischemia/reperfusion (IR) injury. Previous studies have demonstrated that DuraGraft helps maintain endothelial integrity of saphenous vein grafts during ischemic conditions. In this study, we investigated the potential of DuraGraft to mitigate endothelial dysfunction in arterial grafts after IR injury using an aortic transplantation model.

Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1-but not SGLT2-activity correlates with lower risk of heart failure and mortality, therefore additional non-selective SGLT1 inhibition might be beneficial.

Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere.

Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here, we studied 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis, and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations.

Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats.

Background: Heart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes.

Pressure overload-induced systolic heart failure is associated with characteristic myocardial microRNA expression signature and post-transcriptional gene regulation in male rats.

Although systolic function characteristically shows gradual impairment in pressure overload (PO)-evoked left ventricular (LV) hypertrophy (LVH), rapid progression to congestive heart failure (HF) occurs in distinct cases. The molecular mechanisms for the differences in maladaptation are unknown. Here, we examined microRNA (miRNA) expression and miRNA-driven posttranscriptional gene regulation in the two forms of PO-induced LVH (with/without systolic HF).

Preservation solution Custodiol containing human alpha-1-antitrypsin improves graft recovery after prolonged cold ischemic storage in a rat model of heart transplantation.

Introduction: The shortage of available donor hearts and the risk of ischemia/reperfusion injury restrict heart transplantation (HTX). Alpha-1-antitrypsin (AAT), a well-characterized inhibitor of neutrophil serine protease, is used in augmentation therapy to treat emphysema due to severe AAT deficiency. Evidence demonstrates its additional anti-inflammatory and tissue-protective effects.

Alpha-1-Antitrypsin Protects Vascular Grafts of Brain-Dead Rats Against Ischemia/Reperfusion Injury.

Introduction: Endothelial dysfunction is a potential side effect of brain death (BD). Ischemia/reperfusion (IR) injury during heart transplantation may lead to further endothelial damage. Protective effects of alpha-1-antitrypsin (AAT), a human neutrophil serine protease inhibitor, have been demonstrated against IR injury.

Association of Right Ventricular Functional Parameters With Adverse Cardiopulmonary Outcomes: A Meta-analysis.

Aims: We aimed to confirm that three-dimensional echocardiography-derived right ventricular ejection fraction (RVEF) is better associated with adverse cardiopulmonary outcomes than the conventional echocardiographic parameters.

Methods: We performed a meta-analysis of studies reporting the impact of unit change of RVEF, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) on clinical outcomes (all-cause mortality and/or adverse cardiopulmonary outcomes). Hazard ratios (HRs) were rescaled by the within-study SDs to represent standardized changes.

Bone Marrow Culture-Derived Conditioned Medium Recovers Endothelial Function of Vascular Grafts following Ischemia/Reperfusion Injury in Diabetic Rats.

Ischemia/reperfusion injury (IRI) remains a challenge in coronary artery bypass grafting (CABG). Diabetic patients with coronary artery disease are more likely to require CABG and therefore run a high risk for cardiovascular complications. Conditioned medium (CM) from bone marrow-derived mesenchymal stem cells has been shown to have beneficial effects against IRI.

Sex similarities and differences in the reverse and anti-remodeling effect of pressure unloading therapy in a rat model of aortic banding and debanding.

Investigating the effect of sex on pressure unloading therapy in a clinical scenario is limited by several nonstandardized factors. Hence, we sought to study sex-related similarities and differences under laboratory conditions. Pressure overload was induced in male and female rats by aortic banding (AB) for 6 and 12 wk.

Inflammasome activation in end-stage heart failure-associated atrial fibrillation.

Aims: Inflammatory pathways are increasingly recognized as an important factor in the pathophysiology of both heart failure (HF) and atrial fibrillation (AF). However, there is no data about inflammation-related histological and molecular alterations in HF-associated AF. The objective of our study was to investigate inflammatory pathways and fibrosis in end-stage HF-associated AF.

Aspirin Reduces Ischemia-Reperfusion Injury Induced Endothelial Cell Damage of Arterial Grafts in a Rodent Model.

Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a nonsteroidal anti-inflammatory drug improves the long-term patency of vein grafts.

Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia.

Background: Reduced cardiovascular risk in premenopausal women has been the focus of research in recent decades. Previous hypothesis-driven experiments have highlighted the role of sex hormones on distinct inflammatory responses, mitochondrial proteins, extracellular remodeling and estrogen-mediated cardioprotective signaling pathways related to post-ischemic recovery, which were associated with better cardiac functional outcomes in females. We aimed to investigate the early, sex-specific functional and proteomic changes following myocardial ischemia in an unbiased approach.

Graft Preservation Solution DuraGraft Alleviates Vascular Dysfunction Following In Vitro Ischemia/Reperfusion Injury in Rats.

Vascular ischemia/reperfusion injury (IRI) in patients undergoing coronary artery bypass grafting can result in graft failure and the need for repeat revascularization procedures. DuraGraft has been shown to protect structure and function in saphenous vein grafts against IRI. We compared the effect of DuraGraft to saline solution on arterial grafts submitted to IRI.

Novel insights into the athlete's heart: is myocardial work the new champion of systolic function?

Aims: We sought to investigate the correlation between speckle-tracking echocardiography (STE)-derived myocardial work (MW) and invasively measured contractility in a rat model of athlete's heart. We also assessed MW in elite athletes and explored its association with cardiopulmonary exercise test (CPET)-derived aerobic capacity.

Methods And Results: Sixteen rats underwent a 12-week swim training program and were compared to controls (n = 16).

The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following Vascular Ischemia/Reperfusion Injury in Rats.

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI.

AIM2-driven inflammasome activation in heart failure.

Aims: Interleukin-1β (IL-1β) is an important pathogenic factor in cardiovascular diseases including chronic heart failure (HF). The CANTOS trial highlighted that inflammasomes as primary sources of IL-1 β are promising new therapeutic targets in cardiovascular diseases. Therefore, we aimed to assess inflammasome activation in failing hearts to identify activation patterns of inflammasome subtypes as sources of IL-1β.

Conditioned Medium from Mesenchymal Stem Cells Alleviates Endothelial Dysfunction of Vascular Grafts Submitted to Ischemia/Reperfusion Injury in 15-Month-Old Rats.

In patients undergoing coronary artery bypass grafting (CABG), ischemia/reperfusion injury (IRI) is the main contributor to organ dysfunction. Aging-induced vascular damage may be further aggravated during CABG. Favorable effects of conditioned medium (CM) from mesenchymal stem cells (MSCs) have been suggested against IRI.

Left-ventricular hypertrophy in 18-month-old donor rat hearts was not associated with graft dysfunction in the early phase of reperfusion after cardiac transplantation-gene expression profiling.

The use of hearts with left-ventricular (LV) hypertrophy (LVH) could offer an opportunity to extend the donor pool for cardiac transplantation. We assessed the effects of LVH in 18-month-old spontaneously hypertensive stroke-prone (SHRSP) donor rats and following transplantation. In donors, cardiac function and structural alterations were assessed.