Overview of Department Research

Our research faculty members have a wide variety of research interests. Opportunities to do research exist in clinical studies, developing new technologies for clinical application, modeling of diseases, basic science and molecular signaling mechanisms in health and disease.  Our interdisciplinary research efforts are making progress in the areas of cardiovascular diseases, ischemic spinal cord injury, gastrointestinal diseases, second messengers, study of enteric neural circuitry, and central processing of pain. Research opportunities exist in these areas for students, postdoctoral researchers, residents, basic researchers or medical scientists.

 “Patient oriented research” is becoming the main drive of the research efforts of most of our faculty and collaborators, and without exception, all research is focused on clinically relevant questions. In some cases, key clinical questions are being addressed beginning with a clinical study, but often animal models of disease are necessary and used to further study the question, and ultimately, we find our selves turning to basic research, genomic models of disease and molecular signaling studies to better understand the mechanisms. The ultimate challenge we are faced with as medical scientists is to translate our research findings from the laboratory to the clinical setting to benefit our patients. Some of our researchers have been involved in clinical outcome studies that may have direct benefit to patients or are testing or exploring the therapeutic potential of new or improved medicines, or participate in multi-center studies.

 Many projects and some that are funded by the National Institutes of Health are focused on basic research in neurophysiology, cell signaling, purinergic signaling in health and disease, molecular signaling, mechanosensitivity, and genomic models of cardiovascular and intestinal diseases. Overall, research in the department of Anesthesiology has been supported by both local/institutional funds and National agencies including the National Institutes of Health, and particularly Digestive and Kidney Diseases (NIH NIDDK).  We are currently funded by both R01 operating grants and a Clinical Investigator K08 Award from NIDDK.  Other agencies that have been supporting our junior tenure track faculty include the Foundation of Anesthesia and Education Research (FAER), American Society of Anesthesiologists (ASA) and the American Heart Association (AHA, Ohio Chapter). Local funding has come from Strategic Initiative Grants through the College of Medicine & OSU Hospitals. A shared Instrumentation Grant for a Zeiss LSCM imaging system was supported by NIH National Council for Research Resources (NIH NCRR), the Ohio Board of Regents and cost-sharing mechanisms through the office of research in the College of Medicine. A number of grants to external agencies are pending, and several others {R21, R03, or R01’s} or other developmental awards are planned in 2005-2006. Numerous clinical trials have been funded by the Pharmaceutical Industry over the years. The Ohio State Anesthesia Research Foundation (OSARF) is intended to support small starter grants for our faculty doing clinical research.

 Our department was one of the first, if not the first in the College of Medicine, 8 years ago, to have an NIH funded shared-Zeiss Laser Scanning Confocal imaging facility dedicated to the research efforts of NIH funded Investigators in various departments including Anesthesiology, Physiology, Neuroscience, Pharmacology, Vet-Neuropathology and Gastroenterology, and the Heart & Lung Institute. The imaging system is located in the Tzagournis medical Research Facility, and was funded by NIH NCRR, Board of Regents of Ohio and cost-sharing mechanisms at our institution. The principal investigator is Dr. Fievos L. Christofi. The system is set-up for neurophysiological studies integrating electrophysiology, optical imaging of spatio-temporal changes in intracellular Ca²⁺, cyclic AMP, reactive oxygen species or other second messengers in intact ex-vivo tissues {i.e. gut, skeletal muscle, brain slices, dorsal root ganglia, cultured human enterochromaffin cells, glia, neurons}  and in retrogradely identified physiological types of neurons.   

 We are making progress in the use of state-of-the-art-technologies and devices in the clinical setting that may ultimately benefit the patient. Dr. Nadia Nathen’s 3-D echocardiography holds great potential in providing further insights into cardiac function and dysfunction, better predicting surgical outcome, and improving patient care. Drs. Bob Small and Jim Ibenson’s use of functional magnetic resonance imaging (fMRI) should provide new insights into central processing pathways for pain. Roger Dzwonczyk and Carlos DelRio and Dr Mike Howie have developed a cardiac impedence device that was validated in animal models for its applications in assessing improvement in cardiac function after cardiac surgery – It is now FDA approved and it has applications in regional and global ischemia, tissue rejection, edema, and efficacy of tissue preservation techniques.

 At the cellular level, we are also making significant progress in the study and spatio-temporal resolution of alterations in second messengers in neurons or other cells in health and disease, using Laser Scanning Confocal Optical Imaging techniques in combination with several complimentary neurophysiological approaches including electrophysiology, immunofluorescence labeling or neuronal retrograde tracing techniques.

 A newly developed acrolein – derivatized cyclic AMP antiserum developed by Dr. Jorge Guzman in my laboratory as an NIH minority student fellow in the MD/Ph.D training program, is providing new insights into “the polarized projections and morphologies of neurons in an intact mammalian neural circuit”.

 At the sub-cellular genomic level, DNA microarray analysis is being used to study in detail two very distinct processes:

            (1) Screening the efficacy of new potential treatments for Inflammatory Bowel Disease using experimental models of colitis, ileitis or jejunitis.  

            (2) Gene alterations in response to mechanical activation of human enterochromaffin cells – these cells are sparsely located in the gut wall, and are mechanosensitive leading to purine and 5-HT release that is involved in the initiation and propagation of enteric neural reflexes including motility, secretory and vasomotor responses. A review was published recently in News in Physiological Sciences on mechanosensitivity (2003).

 Transgenic modeling of diseases is another strength in  our Anesthesia Research group. Dr. Hamdy Hassanain (Assistant Professor, Anesthesiology & Cardiothoracic surgery, member of DHLI) is an expert at manipulating genes, and has succeeded in developing transgenic mouse models for the study of hypertension, hypotension, wound healing, heart failure, diabetes or smooth muscle hypertrophy. Key aspects of these studies include molecular signaling mechanisms implicated in angiogenesis, remodeling, hypertrophic signaling, and vasculopathies. The role of free radicals in cardiovascular and GI diseases is being studied by targeted mutations in the rac-1 gene linked to NADPH oxidase activity and superoxide anion production in smooth muscle. We are collaborating with faculty in the Dorothy Heart & Lung Institute in Dr. Jay Zweier’s group, and in particular Dr. Arturo Cardounel to study free radicals using spin-trap/Electron Paramagnetic Resonance Imaging (EPRI) in these models and models of Inflammatory Bowel Disease.

 Dr. Mark Gerhardt has had a long-standing interest in ß-adrenergic receptor dysfunction in chronic heart failure and the use of an ovine model of ischemic heart failure is providing new insights into the cellular, molecular, hemodynamic mechanisms involved. The extend to which ß-adrenergic receptor dysfunction occurs in heart failure patients and in those with a Left Ventricular Assist Device (LVAD) is being studied in detail using the sheep model. These ongoing studies are supported by the Federation for Anesthesia & Education Research (FAER) to Dr. Gerhardt (Fievos L. Christofi, Advisor).   

 Drs Hamdy Awad, Hamdy H. Hassanain, Richard Mortensen, Bryan Wolff (Medical Student Fellow) and Fievos L. Christofi are in the process of developing a c-reactive protein (CRP) transgenic model to study its role in heart disease and peripheral vascular disease. This is timely in that recent publications in New England Journal of Medicine (2005) and publication on the front page news of USA today indicate that “lowering blood levels of CRP that may promote artery inflammation is as important as reducing bad cholesterol (LDL) for preventing heart attacks and strokes.” Our studies on the genomic models are being supported by Strategic Initiative Funds from The Ohio State University.  Two transgenic mouse models are in process of validation for high circulating levels of CRP to study the cause and effect relationship in peripheral vascular disease (PVD), heart attack and stroke. 

 Many studies are focused on patient oriented research. An excellent example of patient oriented research is our study of ischemic spinal cord injury leading to paraplegia in patients undergoing aortic cross-clamp and surgical repair of a Thoraco-Abdominal Aortic aneurysm (TAAA). As high as 10-15% of these patients may develop ischemic spinal cord injury and paraplegia, although incidence varies considerably between institutions, and depends on a significant number of variables in patients with a TAAA. A team of investigators headed by Drs Hamdy Awad and Fievos L. Christofi and including Zacharias Suntres (currently an Associate Professor, Lake Head University Medical Center, Thunder Bay, Canada; previously a scientist with National Defense Department), Mike Oglesbee {Professor, Vet-Neuropathologist}, Cynthia Magro {Professor,Pathologist} and Daniel Smeak {Vet-Surgion, Professor & Chair of Small Animal Surgeries} are studying the neural-immune mechanisms linked to ischemic spinal cord injury in TAAA patients. A canine model is suitable to further study T-cell, immune-neural and HSP70 interactions leading ischemic spinal cord injury following aortic cross-clamp/reperfusion injury. This model should prove invaluable in testing new potential therapeutic interventions in reducing or preventing ischemic spinal cord injury. We are beginning to employ genomic models to identify the mechanisms leading to paraplegia. These studies are truly an inter-disciplinary effort to address a key clinical problem puzzling Surgeons and Anesthesiologists for over 40 years. It is hoped that ultimately, this research will benefit the TAAA patient.

 Investigators at OSU-East including Dr. Tom Reilly (Chief of Anesthesia, OSU-East) and Dr Yun Xia have clinical research interests in Regional Anesthesia Techniques. Research in this field will receive further attention in the coming years.

 Other investigators like Dr. Ernesto Goldman, in addition to his clinical studies, he has a long-standing interest in using computer modeling to study age-dependent cardiopulmonary interactions during airway obstruction.  This project is a continuation of an international research program on the cardiovascular impact of respiratory obstruction that he initiated as a Visiting Professor at the University of Buenos Aires, Argentina. He first reported his finding in the Journal of Applied Physiology (1) followed by three abstracts in Anesthesiology.

Dr. Bergese has a long-standing interest in somatosensory evoked potentials in intraoperative procedures. As Chief of Neuroanesthesia, the introduction of the new MRI dedicated to neurosurgery, may provide new opportunities for clinical research in this field that should be explored. 

Medical Students including those in the medical scientist program, residents, undergraduate students, PhD students, postdoctoral students, postdoctoral fellows, research scientists, research associates, research assistants, research nurses, and a clinical engineer complete our Anesthesia research group in the department. In 2004, we had 2 MD/PhD students defend their PhD dissertation: These were Dr. Jim Ibinson and Dr. Jorge Guzman.

The upcoming regular department research meetings is one way to keep our residents, students, staff and faculty up to date on our departmental research activities and should prove useful in further integrating our research efforts. Our CAI residents get an early exposure to research activities in our department through an introductory 1 week research rotation. Later in 3^rd year as CAIII residents, they have an opportunity to do a 6 month research track rotation. This is most suitable for residents interested in Academic Medicine. The possibilities to provide formal training to residents in both clinical and basic research are currently being explored.