DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Making a difference in congenital heart disease

Posted February 25, 2016

Introduction

Congenital heart defects (CHDs) are the most common type of birth defect, occurring in approximately 1% of the babies born each year. Many are mild and do not need treatment, or can be fixed easily, but other CHDs can cause serious health problems or death. CHDs are responsible for one-third of all birth defect-related deaths, and 20% of babies with CHDs who make it through birth will not survive past their first birthday.* The Peer Reviewed Medical Research Program is proud to support congenital heart disease research and in fiscal year 2014 awarded grants supporting the five exciting research projects described below.

Steven A. Fisher, M.D. Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficiency on Fetal Oxygen Metabolism and Congenital Heart Defects
Steven A. Fisher, M.D., University of Maryland, Baltimore

Dr. Fisher is exploring the hypothesis that acute high-altitude hypoxia during critical points of development early in pregnancy reduces oxygen transport and leads to congenital heart defects. He plans to test this hypothesis using a transgenic mouse with a built-in oxygen concentration detector that will allow him to determine at what altitude and developmental stage oxygen delivery to the developing heart is compromised. He will also develop a novel mouse model of placental insufficiency and examine how this condition affects oxygen delivery to fetal tissues under high-altitude hypoxia. The cause of the vast majority of congenital heart defects remains unknown, and Dr. Fisher's work may shed light on one such cause and lead to recommendations and preventative treatments regarding exposure to high altitude during pregnancy.


Nikolay Vasilyev, M.D. Rapidly Deployable Device for Minimally Invasive Dynamic Augmentation of the Ventricular Ejection
Nikolay Vasilyev, M.D., Boston Children's Hospital

Mechanical circulatory support devices are often used to sustain patients with end-stage heart failure when donor organs for transplantation are not available, but they rely on passing blood through an artificial lumen and are associated with significant bleeding/thromboembolic complications. Dr. Vasilyev will design, build, and test a novel implantable intracardiac device that will support circulation with a dynamic pulsatile force timed to the heart contraction. This approach, which would require significantly less anti-coagulation treatment, will use a patient's own ventricular chamber as the pump, and a soft robotic actuator to augment the pumping function of the failed ventricle. Dr. Vasilyev will also develop a method for minimally invasive and rapid insertion of the device using ultrasound guidance.



Cecilia Lo, Ph.D. Respiratory Ciliary Dysfunction and Pulmonary Risks in Congenital Heart Disease Patients
Cecilia Lo, Ph.D., University of Pittsburgh

Dr. Lo has previously found that congenital heart disease patients have a high incidence of ciliary dysfunction, and she plans to test the hypothesis that respiratory ciliary dysfunction in these patients impairs lung function and leads to increased post-surgical respiratory complications and worse outcomes. Pediatric patients about to undergo cardiac surgery will be examined for ciliary function, their respiratory function will be assessed immediately before surgery, and their post-surgical health will be followed for up to 9 months following surgery. The results, should they support the hypothesis, would suggest a benefit to screening congenital heart disease patients for airway ciliary dysfunction prior to surgery and utilizing pulmonary therapy to help reduce post-surgical respiratory complications.


Scott Fahrenkrug, Ph.D. Exogenic Human Heart in Gene-Edited Animals
Daniel Garry, M.D., Ph.D., University of Minnesota; Scott Fahrenkrug, Ph.D., Recombinetics, Inc.

Dr. Garry and Dr. Fahrenkrug are working together to create an exogenic (originating outside the organism) human heart in pigs. They plan to develop a porcine animal model where host genes for cardiogenesis are knocked out and human stem cells are utilized to produce a humanized heart in the pig embryo. If successful, the animals will serve as a platform to study the regenerative potential of the human heart and to test responses to pharmacological agents or novel devices and may also one day serve as an organ source for orthotopic heart transplantation into humans.




Thomas Barker, Ph.D. Development of Platelet-Like Particles for Augmentation of Hemostasis in Congenital Heart Defect Patients at High Risk for Bleeding during Cardiac Surgery
Thomas Barker, Ph.D., Georgia Tech Research Corporation

Bleeding is a frequent complication of surgery involving cardiopulmonary bypass and, while reduced usage of blood products has been shown to correlate with better patient outcomes, few alternatives to transfusion exist. Dr. Barker is part of a team that recently developed synthetic platelet-like particles (PLPs), which share many features with natural platelets, including augmentation of clotting and clot contraction over time. He plans to optimize the formulation of the PLPs and demonstrate that they can decrease bleeding times in animal models that recapitulate the bleeding problems associated with cardiopulmonary bypass.



Links:

Abstracts for Dr. Fisher
Public and Technical Abstracts: Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficiency on Fetal Oxygen Metabolism and Congenital Heart Defects

Abstracts for Dr. Vasilyev
Public and Technical Abstracts: Rapidly Deployable Device for Minimally Invasive Dynamic Augmentation of the Ventricular Ejection

Abstracts for Dr. Lo
Public and Technical Abstracts: Respiratory Ciliary Dysfunction and Pulmonary Risks in Congenital Heart Disease Patients

Abstracts for Dr. Garry
Public and Technical Abstracts: Exogenic Human Heart in Gene-Edited Animals

Abstracts for Dr. Fahrenkrug
Public and Technical Abstracts: Exogenic Human Heart in Gene-Edited Animals

Abstracts for Dr. Barker
Public and Technical Abstracts: Development of Platelet-Like Particles for Augmentation of Hemostasis in Congenital Heart Defect Patients at High Risk for Bleeding during Cardiac Surgery

* Source: www.childrensheartfoundation.org

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Last updated Friday, February 26, 2016