Animal Model & Clinical Core

Florida International University, Miami FL

Investigators

Linked publications & trials

Abstract

ABSTRACT: Core C is designed to provide PPG investigators with rigorously defined and reproducible novel ovine models of congenital heart disease (CHD) using fetal cardiac surgical techniques. To this end, Core C will comprehensively generate, manage, and provide all animal-related experiments, resources, and expertise. In addition, Core C has previously obtained peri-operative blood samples from neonates, infants, children, and adults with a wide range of differing congenital heart defects that can be utilized by PPG investigators. A secure database has already been established that contains banked samples and clinical data on >500 patients. Core C will be defined in this context by providing five services: 1) Ovine models of CHD. This will include our well- established Shunt model and our newly created Post Shunt Closure model. Tissues (peripheral lung and isolated vessels) and primary pulmonary artery endothelial and smooth muscle cells (both proximal and microvascular) will be available to PPG investigators. 2) Acquisition and analysis of data. This will include the evaluation of invasive and non-invasive cardiopulmonary hemodynamics, including sophisticated ventricular function indices, pulmonary vascular reactivity (both in vivo and ex vivo), the assessment of pulmonary vascular remodeling, advanced in vivo imaging, that includes echocardiography, computed tomography (CT) and MRI cardiopulmonary imaging, cardiac catheterization, formal pulmonary function testing, and cardiopulmonary exercise testing. 3) Biochemical, proliferation, apoptosis, and angiogenesis determinations. This will include the measurement of various reactive oxygen, nitric oxide metabolites (NOx) and nitrogen species of oxygen or nitrogen oxide in vascular cells and tissues, indices of cell proliferation, apoptosis, and tube formation. 4) Use of medicinal chemistry to generate novel therapeutic agents. 5) A biorepository and corresponding clinical database of neonates, infants, children, and adults with CHD. Blood samples from patients with CHD were obtained before and after surgical repair for human confirmation of aberrant pathways initially identified in animals and for metabolic screening. Correlation between the identified aberrations, with the type of CHD (+/- flow; +/- pressure), and the degree of pre-operative and post-operative pulmonary vascular disease will be sought. Core C will enhance the scientific work for all three projects by assuring that all animal models are standardized and performed uniformly by highly experienced and trained personnel. Tissues and cells from these models will also be used for bulk and single-cell transcriptomics. Investigators with many years of experience using these techniques run Core C. They have developed or adapted several techniques and applied them to perform physiological studies in vitro, ex-vivo, and in vivo systems. As a central dedicated analytical resource, Core C will ensure that these analyses are carried out cost-efficiently with minimal animal morbidity and mortality. Sex as a biological variable will also be explored throughout the Core.