Metabolic gene therapy in a canine with pulmonary hypertension secondary to degenerative mitral valve disease.

Myxomatous mitral valve disease (MMVD) stands out as the most prevalent acquired canine heart disease. Its occurrence can reach up to 40% in small breed dogs and escalates in geriatric canine populations. MMVD leads to thickening and incomplete coaptation of valve leaflets during systole, resulting in secondary mitral valve regurgitation.

Predictors of Neurologic Complications and Neurodevelopmental Outcome in Pediatric Cardiac Surgery With Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) has emerged as an important intervention for children both preceding and following cardiac surgery. There is a notable lack of comprehensive information regarding neurodevelopmental outcomes. The Norwood procedure and complex biventricular repairs exhibit the highest prevalence of ECMO usage.

Hypoxia-Induced Piglet Model of Cardiac Arrest with Assisted Resuscitation by Extracorporeal Membrane Oxygenation.

The mortality rate of newborns with severe congenital heart disease (CHD) has significantly decreased over the past few decades. However, many of these children experience neurological impairments, particularly following a hypoxic cardiac arrest. The use of extracorporeal membrane oxygenation (ECMO) has been considered an effective treatment for severe hypoxia in CHD cases.

Unilateral Lung Removal in Combination with Monocrotaline or SU5416 in Rodents: A Reliable Model to Mimic the Pathology of the Human Pulmonary Hypertension.

Pulmonary hypertension (PH) is a chronic and progressive disorder characterized by elevated mean pulmonary arterial pressure, pulmonary vascular remodeling, and the development of concentric laminar intimal fibrosis with plexiform lesions. While rodent models have been developed to study PH, they have certain deficiencies and do not entirely replicate the human disease due to the heterogeneity of PH pathology. Therefore, combined models are necessary to study PH.

Effects of Hormone Replacement Therapy on Women's Lung Health and Disease.

This review provides an overview of menopausal hormone therapy and pulmonary disease risk, with a focus on the effect of hormone replacement therapy (HRT) on pulmonary function and its relation to lung diseases. This summary is based on authors' knowledge in the field of HRT and supplemented by a PubMed search using the terms "menopause hormone therapy," "asthma", "lung cancer", "chronic obstructive pulmonary disease", "lung function", and "pulmonary hypertension". Available evidence indicates that there is limited research on the role of sex hormones in the susceptibility, severity, and progression of chronic respiratory diseases.

Chronic thoracic pain after cardiac surgery: role of inflammation and biomechanical sternal stability.

Introduction: The pathogenesis of chronic chest pain after cardiac surgery has not been determinate. If left untreated, postoperative sternal pain reduces the quality of life and patient satisfaction with cardiac surgery. The purpose of the study was to examine the effect of chest inflammation on postoperative pain, risk factors for chronic pain after cardiac surgery and to explore how chest reconstruction was associated with the intensity of pain.

Acid ceramidase gene therapy ameliorates pulmonary arterial hypertension with right heart dysfunction.

Background: Up-regulation of ceramides in pulmonary hypertension (PH), contributing to perturbations in sphingolipid homeostasis and the transition of cells to a senescence state. We assessed the safety, feasibility, and efficiency of acid ceramidase gene transfer in a rodent PH model.

Methods: A model of PH was established by the combination of left pneumonectomy and injection of Sugen toxin.

Surgical Methods for Cardiac Gene Delivery in Large Animals.

This chapter describes main strategies of surgical gene delivery in large animals. Existing methods of cardiac gene transfer can be classified by the site of injection, interventional approach, and type of cardiac circulation at the time of transfer. Randomized clinical trials have suggested that the therapeutic benefits of gene therapy are not as substantial as expected from animal studies.

Cardiac Targeted Adeno-Associated Virus Injection in Rats.

Gene therapy is a promising approach in the treatment of cardiovascular diseases. The vectors available for cardiovascular gene therapy have significantly improved over time. Cardiac tropism is a primary characteristic of an ideal vector along with a long-term expression profile and a minimal risk of cellular immune response.

Efficient cardiac gene transfer and early-onset expression of a synthetic adeno-associated viral vector, Anc80L65, after intramyocardial administration.

Objective: Gene therapy is a promising approach in the treatment of cardiovascular diseases. Preclinical and clinical studies have demonstrated that adeno-associated viral vectors are the most attractive vehicles for gene transfer. However, preexisting immunity, delayed gene expression, and postinfection immune response limit the success of this technology.

Right predominant electrical remodeling in a pure model of pulmonary hypertension promotes reentrant arrhythmias.

Background: Electrophysiological (EP) properties have been studied mainly in the monocrotaline model of pulmonary arterial hypertension (PAH). Findings are confounded by major extrapulmonary toxicities, which preclude the ability to draw definitive conclusions regarding the role of PAH per se in EP remodeling.

Objective: The purpose of this study was to investigate the EP substrate and arrhythmic vulnerability of a new model of PAH that avoids extracardiopulmonary toxicities.

Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a devastating lung disease characterized by the progressive obstruction of the distal pulmonary arteries (PA). Structural and functional alteration of pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) contributes to PA wall remodeling and vascular resistance, which may lead to maladaptive right ventricular (RV) failure and, ultimately, death. Here, we found that decreased expression of sarcoplasmic/endoplasmic reticulum Ca ATPase 2a (SERCA2a) in the lung samples of PAH patients was associated with the down-regulation of bone morphogenetic protein receptor type 2 (BMPR2) and the activation of signal transducer and activator of transcription 3 (STAT3).

Inflammatory Responses with Left Ventricular Compromise after Induction of Myocardial Infarcts in Sheep (Ovis .

Ischemic myocardial disease is a major cause of death among humans worldwide; it results in scarring and pallor of the myocardium and triggers an inflammatory response that contributes to impaired left ventricular function. This response includes and is evidenced by the production of several inflammatory cytokines including TNFα, IL1β, IL4, IFNγ, IL10 and IL6. In the current study, myocardial infarcts were induced in 6 mo old male castrated sheep by ligation of the left circumflex obtuse marginal arteries (OM 1 and 2).

Use of longitudinal rigid sternal fixation in prevention and treatment of wound complications among high-risk patients after cardiac surgery.

Background: Traditionally, wire cerclage closure has been used to reapproximate the sternum after cardiac surgery. Recent evidence suggests that rigid sternal fixation may reduce the risk of wound complications. The aim of this study was to analyze our 10-year experience with longitudinal rigid sternal fixation (LRSF) for prevention and treatment of wound complications in high-risk patients.

Advantages of intraoperative implantation of Impella 5.5 SmartAssist in the Management of Acute Post-Infarction Ventricular Septal Defect with cardiogenic shock.

Background: Despite advances in surgical techniques and aggressive therapy of post-infarction ventricular septal defect (VSD) with cardiogenic shock, the overall morbidity and mortality is frustratingly high. The Impella 5.5 SmartAssist (Abiomed, Danvers, MA) is a surgically implanted temporary device, recently approved by the FDA ( https://www.

Median Sternotomy After Sternal Reconstruction With Bilateral Longitudinal Plating in a Patient With Osteoporosis.

In recent decades, new information has arisen regarding sternal healing and extended indications for using rigid plate fixation in patients during cardio-thoracic procedures. Three randomized controlled multicenter clinical trials recently demonstrated positive results after rigid plate fixation, including reduced sternal complications and decreased length of hospital stay. However, redo-sternotomy after sternal reconstruction utilizing rigid fixation has not been previously delineated in surgical literature.

Successful Transduction with AAV Vectors after Selective Depletion of Anti-AAV Antibodies by Immunoadsorption.

Gene therapy with adeno-associated virus (AAV)-based vectors shows great promise for the gene therapeutic treatment of a broad array of diseases. In fact, the treatment of genetic diseases with AAV vectors is currently the only gene therapy approach that is approved by the US Food and Drug Administration (FDA). Unfortunately, pre-existing antibodies against AAV severely limit the patient population that can potentially benefit from AAV gene therapy, especially if the vector is delivered by intravenous injection.

Altering Sphingolipid Metabolism Attenuates Cell Death and Inflammatory Response After Myocardial Infarction.

Background: Sphingolipids have recently emerged as a biomarker of recurrence and mortality after myocardial infarction (MI). The increased ceramide levels in mammalian heart tissues during acute MI, as demonstrated by several groups, is associated with higher cell death rates in the left ventricle and deteriorated cardiac function. Ceramidase, the only enzyme known to hydrolyze proapoptotic ceramide, generates sphingosine, which is then phosphorylated by sphingosine kinase to produce the prosurvival molecule sphingosine-1-phosphate.