Endothelialization of coronary stents after intra-luminal adenoviral VEGF-A gene transfer in a preclinical porcine restenosis model - Studies with optical coherence tomography, angioscopy, multiphoton and scanning electron microscopy.

Background: Coronary stenting operations have become the main option for the treatment of coronary heart disease. Vessel recovery after stenting has emerged as a critical factor in reducing possible complications. In this study, we evaluated the feasibility, safety and efficacy of locally administered intraluminal gene therapy delivered using a specialized infusion balloon catheter.

Adenoviral VEGF-D gene therapy for myocardial ischemia.

Cardiovascular diseases are the leading cause of death globally. In spite of the availability of improved treatments, there is still a large group of chronic ischemia patients who suffer from significant symptoms and disability. Thus, there is a clear need to develop new treatment strategies for these patients.

Quantification of Myocardial Blood Flow by Machine Learning Analysis of Modified Dual Bolus MRI Examination.

Contrast-enhanced magnetic resonance imaging (MRI) is a promising method for estimating myocardial blood flow (MBF). However, it is often affected by noise from imaging artefacts, such as dark rim artefact obscuring relevant features. Machine learning enables extracting important features from such noisy data and is increasingly applied in areas where traditional approaches are limited.

Susceptibility to Cardiac Arrhythmias and Sympathetic Nerve Growth in VEGF-B Overexpressing Myocardium.

VEGF-B gene therapy is a promising proangiogenic treatment for ischemic heart disease, but, unexpectedly, we found that high doses of VEGF-B promote ventricular arrhythmias (VAs). VEGF-B knockout, alpha myosin heavy-chain promoter (αMHC)-VEGF-B transgenic mice, and pigs transduced intramyocardially with adenoviral (Ad)VEGF- B186 were studied. Immunostaining showed a 2-fold increase in the number of nerves per field (76 vs.

Evaluation of Biodegradable Stent Graft Coatings in Pig and Rabbit Models.

Aims: Percutaneous coronary intervention is routinely performed to treat occlusive coronary artery disease. Coronary perforation is a potential complication and can be treated with a stent graft. Current stent grafts are associated with high restenosis rates.

Quantification of porcine myocardial perfusion with modified dual bolus MRI - a prospective study with a PET reference.

Background: The reliable quantification of myocardial blood flow (MBF) with MRI, necessitates the correction of errors in arterial input function (AIF) caused by the T1 saturation effect. The aim of this study was to compare MBF determined by a traditional dual bolus method against a modified dual bolus approach and to evaluate both methods against PET in a porcine model of myocardial ischemia.

Methods: Local myocardial ischemia was induced in five pigs, which were subsequently examined with contrast enhanced MRI (gadoteric acid) and PET (O-15 water).

Assessment of myocardial viability with [O]water PET: A validation study in experimental myocardial infarction.

Background: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI).

Methods And Results: Pigs underwent resting [O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery.

Imaging of αβ integrin expression in experimental myocardial ischemia with [Ga]NODAGA-RGD positron emission tomography.

Background: Radiolabeled RGD peptides detect αβ integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [Ga]NODAGA-RGD detects increased αβ integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αβ integrin is expressed in viable ischemic or injured myocardium.

Methods: We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery.

AdVEGF-B186 and AdVEGF-DΔNΔC induce angiogenesis and increase perfusion in porcine myocardium.

Objective: Coronary heart disease remains a significant clinical problem, and new therapies are needed especially for patients with refractory angina for whom the current therapies do not provide sufficient relief. The aim of this study was to find out if angiogenic gene therapy using new members of the vascular endothelial growth factor (VEGF) family, VEGF-B and VEGF-D, increase myocardial perfusion as measured by the positron emission tomography (PET) O-imaging, and whether there would be coronary steal effect to the contralateral side. Furthermore, safety of intramyocardial angiogenic adenoviral gene transfer was evaluated.

Current gene therapy trials for vascular diseases.

Introduction: In the previous gene therapy trials for vascular diseases, safety of the therapies has been demonstrated with some evidence for clinical benefits. In the future, it will be important to also test the potential clinical benefits of the treatments in randomized and controlled trials with sufficient numbers of patients.

Areas Covered: This review covers 15 currently ongoing cardiovascular gene therapy trials that aim to treat coronary artery disease, heart failure and peripheral artery disease.

The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs.

A large animal model of chronic myocardial ischemia and heart failure is crucial for the development of novel therapeutic approaches. In this study we developed a novel percutaneous one- and two-vessel model for chronic myocardial ischemia using a stent coated with a polytetrafluoroethylene tube formed in a bottleneck shape. The bottleneck stent was implanted in the proximal left anterior descending (LAD) or proximal circumflex artery (LCX), or in both proximal LCX and mid LAD 1 wk later (2-vessel model), and pigs were followed for 4-5 wk.