The Newsletter of CIRCL, the Center for Injury Research & Control at the University of Pittsburgh
Volume 11, Issue 1: Spring 2008
The Safar Center for Resuscitation Research (web site)
Patrick M. Kochanek, MD, Director, Safar Center
The Safar Center for Resuscitation Research is a unique facility housed within the Department of Critical Care Medicine at the University of Pittsburgh School of Medicine. The Center's mission is to identify and promote ever-improving methods of preventing premature death and reducing associated disability for trauma and cardiac arrest in people with “hearts and brains too good to die.” The Center is truly multidisciplinary, houses investigators from the Departmentts of Neurosurgery, Physical Medicine and Rehabilitation, Surgery, and Pediatrics, and its faculty collaborates with a vast array of investigators world-wide.
Clinician and Scientists working at the Safar Center have the special honor of following in the footsteps of the late Distinguished Professor of Resuscitation Medicine, Dr. Peter Safar, recognized as the “father of CPR.” Many of the faculty at the Safar Center had the great fortune of knowing Dr. Safar, learning from his experience, and--to this day--being driven by the incredible passion and purpose that he brought to the Center each day. Peter Safar often said “How is your research relevant to the patient; how will it change practice?” His mandate for patient-oriented research—whether at the bench or bedside is a central theme of our Center’s work in addressing “resuscitation medicine” in its broadest context.
While much of basic science research in medicine over the past 30 years has moved toward simplifying systems, such as with tissue culture or very simple models, much of the work at the Safar Center has focused on the development and use of highly clinically relevant “super models.” For example, several projects at the Center that are funded by the National Institutes of Child Health and Human Development and Neurological Disorders and Stroke (NICHD and NINDS, respectively) are targeting the development of new therapies for cardiac arrest in children—a condition that often results from asphyxiation in conditions such as drowning. Studying cardiac arrest in tiny developing 17 day-old rats, Safar Center investigators use highly clinically relevant paradigms that include chest compressions and standard resuscitation drugs such as epinephrine, rather than using “simple models” that produces isolated brain damage in a somewhat contrived and less clinically relevant manner. Similarly, in studies funded by the United States Army, Safar Center Investigators are modeling blast-induced traumatic brain injury and poly-trauma using a mouse model of traumatic brain injury followed by hemorrhagic shock. In that model, mice are monitored similar to patients in intensive care, and resuscitation phases modeling “field” and “in-hospital” care are incorporated, producing a highly clinically relevant scenario. Similarly, an investigative team at the Center uses cardiopulmonary bypass in rats to study emergency preservation strategies modeling an otherwise lethal traumatic exsanguination. An important and unique facet of work at the Center is that these highly clinically relevant studies have been able to be accomplished in small animals such as mice and rats—species for which important molecular and genetic tools are available for state-of-the-art investigation. This approach, however, requires tremendous technical expertise—a luxury that Safar Center investigators are afforded, given the superb cadre of experienced and talented technicians that wok at the Center, many of whom have over 20 years of experience. Finally, in the laboratory, Safar Center investigators were also recently selected by the Defense Advanced Research Projects Agency (DARPA) of the U.S. Department of Defense, to collaborate with investigators at Walter Reed Army Institute for Research, Yale, and Harvard, in an important project (PREVENT BLAST) focused on blast-induced traumatic brain injury—a critical problem in the Iraq war and emerging problem in civilian terrorism.
Clinical research is also a vital component of the research underway by Safar Center investigators. This includes both projects originating in the Center and those that involve collaboration. Some of this clinical research is supported by CIRCL. In studies funded by NINDS, Dr. Robert Clark has lead a team of scientists carrying out arguably the most extensive investigation of cellular and molecular mechanisms involved in the evolution of neuronal death in the human brain after traumatic brain injury. Those studies have investigated both adults and children and have been carried out in collaboration with a variety of University of Pittsburgh faculty across many departments. Some of those studies have taken advantage of the important work on therapeutic hypothermia. Funded by a new grant from the United States Army, Dr. Samuel Tisherman is coordinating a multi-center trial of the aforementioned novel emergency preservation approach for victims of otherwise lethal exsanguination cardiac arrest from trauma. That study uses an emergency induction of deep hypothermia to buy time for surgical repair of the victim, followed by delayed resuscitation. Finally, a number of clinical projects at the Center have focused on the study of biomarkers and bio-mediators of brain injury in both children and adults with traumatic brain injury and cardiac arrest. Two of those projects involve work supported, in part, by CIRCL. Dr. Rachel Berger is testing serum biomarkers of brain injury to help pediatricians and emergency medicine physicians in making the difficult diagnosis of inflicted childhood Neurotrauma—often called “shaken baby syndrome.” Similarly, Dr. Amy Wagner is studying cerebrospinal fluid and serum markers of the hormonal response to severe traumatic brain injury in work that has taken on special relevance given some of the promising laboratory and clinical evidence for a possible role of progesterone therapy for human head injury.
Finally, the Safar Center is a hotbed of training young investigators who are interested in resuscitation-related work, particularly in the areas of traumatic brain injury and cardiac arrest. A T-32 grant from NICHD titled “Pediatric Neurointensive Care and Resuscitation Research” is an important infrastructure in this regard. However, the Safar Center is a vital training resource for many Departments including Critical Care Medicine, Physical Medicine and Rehabilitation, and Pediatrics among others.