Terry Elton, PhD, Interim Director
The OSUMC’s Dorothy M. Davis Heart and Lung Research Institute (DHLRI) is
one of the nation’s few free-standing facilities devoted entirely to studying diseases of the heart, lungs and blood vessels. Its mission is to develop strategies to prevent and cure heart and lung diseases. The DHLRI is an internationally recognized center of excellence for medical research that can be broadly applied to other diseases and conditions.
Ongoing Research Programs
Four major thematic areas:
- Myocardial ischemia and metabolism
- Myocyte biology and disease
- Inflammation, fibrosis and immune function
- Regenerative medicine
Sub-areas of specialized focus include:
Cardiovascular and molecular imaging
- Cardiovascular genomics and pharmacogenomics
- Myocardial salvage and regeneration post myocardial
infarction
- Molecular therapies and devices for treating heart failure
- Fibrosis, remodeling and lung injury
- Innate immune system function
- Mitochondria biology and critical care disease
- Control of lung inflammation to prevent lung fibrosis
- Environmentally and smoking-induced heart and lung disease
- Tissue engineering and stem cell biology
- Nitric oxide biology and signaling
- Redox biology and free radical research
- Molecular and cellular therapies of tissue repair and wound
healing
Research Accomplishments of 2007
- The postischemic heart exhibits a loss of vasodilatory function due to alterations in nitric oxide synthase (NOS). Scientists observed for the first time that the critical NOS cofactor
tetrahydrobiopterin (BH4) is depleted during myocardial ischemia, causing a loss of production of the endothelialderived relaxing factor nitric oxide. They then developed
liposomal formulations of BH4 that restored coronary vasodilation, providing a promising new approach to reverse endothelial dysfunction in acute coronary syndromes.
- Scientists developed an MRI technique enabling real-time noninvasive measurement of myocardial cell death during myocardial infarction. This technique should enhance
development of new therapeutic approaches to salvage heart muscle at risk in acute myocardial infarction.
- Scientists developed technology and instrumentation to enable the in vivo imaging of free radicals using combined electron paramagnetic resonance (EPR)- and nuclear magnetic
resonance (NMR)-based magnetic resonance imaging (MRI). This allows the first in vivo mapping of free radicals and their metabolism in animal models of disease.
- The first phase I trial using an adenoviral gene transfer approach to induce angiogenesis with hypoxia inducible factor in peripheral arterial disease demonstrated safety and allowed assessment of limited efficacy, paving the way for a large phase II trial being conducted in the United States and Europe.
- Research led to the first identification that abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel are linked to exercise-induced sudden cardiac death.
- Researchers were the first to label stem cells with oxygensensing nanoprobes and use in vivo EPR technology to monitor tissue oxygenation in the infarct myocardium before and after treatment with transplanted stem cells. These studies, using an animal model of heart attack, demonstrated noninvasive monitoring of tissue oxygenation for weeks after cell therapy. The results showed a significant enhancement of myocardial oxygenation at the site of cell transplantation.
- Scientists demonstrated that sustained reverse left ventricular structural remodeling, at one year, can be achieved with cardiac resynchronization, and that this efficacy is a function of heart failure etiology.
- Investigators studied the efficacy and safety of hemodynamic monitoring devices that lead to improved treatment outcomes for patients with heart failure. They also participated in clinical trials for the HeartPod (Savacor, Inc), Wireless Pressure Sensor (CardioMEMS, Inc) and Chronicle ICD (Medtronic, Inc.). Feasibility and pivotal studies of these novel technologies were performed in collaboration with DHLRI heart failure specialists and electrophysiologists.
- Researchers in the multidisciplinary Sleep-Heart Program investigate questions about cardiovascular consequences of sleep disorders. The program examines translational and
clinical questions with focus on the relation between respiratory disorders of sleep and cardiovascular diseases. In 2007, studies included: prevalence and clinical outcomes of sleep apnea in patients with heart failure; evaluating sleep treatments in cardiac patients; and consequences of oxidative stress in sleep apnea.
- In the lung emphysema treatment trial, DHLRI pulmonary physicians found that patients with advanced emphysema who did not have symptom resolution with rehabilitation did
better with lung volume reduction surgery than with medical treatment.
- The DHLRI Intramural Thematic Grants Program was established
to encourage and support investigators in developing
programs and careers in the four thematic research areas of
emphasis and growth. During the summer/fall of 2007, nine
investigators were funded for a total of $494,010.
OSU Dorothy M. Davis Heart and Lung Research Institute
473 W. 12th Avenue
Columbus, OH 43210
(614) 247-7766