ANIMAL RESOURCES MANAGEMENT In addition to the surgery and phenotyping cores, the NHLBI animal program provides veterinary care, research technical support and animal husbandry to rodents in NHLBI operated facilities and oversight of NHLBI animal activities in other NIH facilities. This includes logistical and financial management as well as regulatory compliance for all NHLBI animal activities. Dr. Hawkins, Dr. Springer and Ms. Joni Taylor also serve as members of the NHLBI Animal Care and Use Committee which is responsible for the research use and regulatory compliance of the animal research activities. Drs Hawkins and Springer and the program managers also assist investigators in the planning of research projects, preparation of animal protocols and implementation of the work. SURGERY CORE SCIENTIFIC IMPACT NHLBI Directors Awards, December 2014 Dr. Hong San as part of a group award to Dr. Manfred Boehms lab for identifying a biological pathway that contributes to the high rate of vein graft failure following bypass surgery. Dr. Hawkins as part of group award to Dr. Yosuke Mukoyamas lab for elucidation the patterning mechanisms responsible for generating branched neuro-vascular wiring networks during organogenesis. Joni Taylor and Kathy Lucas as part of a group award to Dr. Han Wens lab for for outstanding work on x-ray phase contrast imaging Orloff Award January 2015 Karen Keeran and Gayle Nugent as part of a group award to Drs. Stew Levine and Jay Chung for A Potential New Target for the Treatment of Asthma. Xenotransplant studies: Transplanting pig hearts into baboons. This study has led to new treatments to prevent rejection. This study has established records for animal survival post-transplant Stem cell therapy: This is for repair of damaged heart tissue using pigs. Bone marrow transplantation: Development of a pressure-mediated bone marrow transplant delivery system using pigs. This will allow bone marrow transplants to be made directly in the bone. When given IV, many of the cells are lost in circulation. This model has now been moved to NHPs, this is the next logical step towards moving this technique in to clinical trials. NIH has a patent application pending for this device listing ASR staff Randy Clevenger and Tim Hunt as some of the co-inventors. Drs. Childs, Hoyt and Pantin. Pathogenesis of asthma: This work has identified that a protein responsible for mediating responses to bacterial infection is also part of the asthmatic response to house dust mites. Dr. S. Levine. Heart valve replacement: Many patients who need heart valve replacement are too sick for surgery. This study has developed a method for replacing defective heart valve via a trocar, under real time MRI, in pigs. Dr. Horvath. Response to injury in blood vessels: Dr. San has provided mouse models of vascular injury including a model of internal injury using a fine wire. This helps with basic understanding of the development of atherosclerosis. Dr. Boehm Failure of vein grafts: Dr. San has performed many vein grafts in mouse models which has been an important part in research to understand why vascular grafts fail. This has resulted in a recent publication in Science Translational Medicine. Dr. Boehm Myocardial injury: Dr. San performs myocardial infarct surgery to allow for basic science studies of the response of heart muscle to injury and treatment with stem cells for Dr. Boehm. ASR staff also performed myocardial infarcts in rats and mice for Drs. Arai and Hoyt Mitochondrial function in diabetes and heart disease: Dr. San performs an aortic banding procedure in the thorax of mice. This is an incredibly difficult surgery. Dr. Sack Intra-cerebral injections in mice: Randy Clevenger and Karen Keeran have mastered the skills to provide precise injections into specific areas of a mouse brain as part of a new project to study Parkinsons disease. Dr. Sack Cerebral ischemia (stroke) in mice. This is evaluating the response of various lines of mice to a surgical model of ischemic stroke. Randy Clevenger has mastered the technique and is training other techs in the procedure. Drs. Moss, Remaley & Amar. Non-surgical heart cavity access: Many structural heart diseases require surgery for definitive treatment. The goal is to develop a method of accessing the heart through the chest by needle puncture under MRI guidance, then advancing a large bore tube that will enable the delivery of large appliances to the heart without surgery. Drs. Lederman and Halabi X-Ray Fused with MRI (XFM): Investigating cardiac MRI soft-tissue depiction overlaid on conventional X-Ray to guide transcatheter structural heart therapy in a safer, more effective way with less radiation exposure. Drs. Lederman and Ratnayak Mitochondrial organization and dynamics: Employing confocal and multi-photon microscopy on a transgenic mouse line expressing a mitochondrial-targeted, photoactivatable GFP, has enabled the characterization of mitochondrial structure and motion in vivo. This mouse model and advanced imaging technique will permit examination of the mitochondrial response to physiological perturbations, such as ischemia-reperfusion, in live animals. Dr. Balaban Mouse models of Atherosclerosis: Development of in situ, aortic microdissection protocols in transgenic neonatal and adult mice for multiphoton microscopy and histopathology. This study has allowed for longitudinal, 3-dimensional characterization of the extracellular matrix in the developing vascular bed of healthy and diseased mice. This work will contribute to future investigations into the pathogenesis of human atherosclerotic disease and piloting therapeutic interventions. Drs. Balaban and Zadrozny We are developing new ways to image myocardial infarctions. Some of these methods are suitable for use in diagnosing heart disease in patients. Ms. Taylor performs the surgery and Shawn Kozlov is learning the procedure. Dr. Arai. Identification of LDL-binding proteins in aortic valve and arterial wall will help in the development of new drugs to prevent atheroslerotic lesion formation. Studies conducted using pig tissues. Drs. Neufeld and Balaban.
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