Research in Special Environments at the University at Buffalo

CRESE investigators are using an air pressurization chamber to simulate the effects of blood loss in patients. Photo by Douglas Levere

By Dr. David Hostler and Dr. David R. Pendergast

THE CENTER FOR RESEARCH AND EDUCATION IN SPECIAL ENVIRONMENTS AND ITS FACILITIES A THE UNIVERSITY AT BUFFALO HAVE BEEN AT THE FOREFRONT OF MEDICAL RESEARCH FOR THOSE WHO WORK BOTH ABOVE AND BELOW THE SEA.

Although the Center for Research and Education in Special Environments (CRESE) at the State University of New York (SUNY) at Buffalo was formally established as an organized research center in 1990, its lineage dates back to the 19th century and its collaboration with the Office of Naval Research (ONR) dates to the 1960s.

The medical school in Buffalo was established in 1846. It was believed at the time that a better medical system was needed to meet the demands of a city growing in prominence. The Department of Physiology, the original home of CRESE, was established with the medical school and has operated continuously ever since. At that time, Buffalo was emerging as one of the most important commercial cities in the United States, transshipping goods from the Midwest to the East Coast and providing a waypoint for settlers from the east to the west. Over the next century, the medical school was joined by additional schools and departments to become a comprehensive private university, which later joined the SUNY system.

The development of the school as a full-fledged academic center led to the recruitment of Dr. Herman Rahn as chair of physiology in 1956. Rahn was joined by Dr. Leon Farhi and retired Capt. Edward Lanphier to reset the research program of the department toward environmental physiology and a future collaboration with ONR. This trio responded to a national request for proposals to create “super laboratories” of excellence. The University at Buffalo submitted a proposal to establish a laboratory with a focus on thermal stress, exercise, altered gravity, and hyper/hypobaric environments in 1966. The laboratory was supported by the Department of Defense (DoD) and ONR as the National Laboratory of Environmental Physiology. The award was termed the “Themis Project.” The center was nearly abandoned before it began, however, when the university’s partnership with the Defense Department attracted the attention of anti-Vietnam War protests. The faculty senate voted in support of the student protesters to have the president of the university refuse the funding for Themis, so the project was delayed for another two years.

Ultimately, the University at Buffalo erected a building and the DoD and ONR financed the purchase of major equipment including a human centrifuge and hyper/ hypobaric chambers. In 1972, a running track, high- pressure chamber, exercise laboratory, and biochemical laboratories were installed to complete the facility. Lanphier would later move the original hyperbaric chamber to the University of Wisconsin at Madison to establish an ONR-supported program performing hyperbaric work in goat and sheep models of decompression illness. That laboratory is still operating today under the direction of Drs. Marlowe Eldridge and Aleksey Sobakin.

CRESE flourished thanks to the original ONR funding. The infrastructure in the lab allowed investigators to further support the Navy by performing studies that were supported by Naval Sea Systems Command to solve practical issues as well as concentrate on more basic and applied science projects for ONR. The human centrifuge allowed the investigators to perform preliminary work simulating changes in gravity, which resulted in the Space Shuttle Scientific Project (#066 on STS 40 and 41) supported by the National Aviation and Space Administration.

Since its establishment, CRESE has been self-sustaining and productive. Replacement costs are estimated to exceed $40 million. It is unlikely that a similar center will ever be built again, making it critical to the National Naval Responsibility Initiative in undersea medicine. The initial funding and continued ONR support in maintaining the CRESE facilities has allowed the center to leverage its position and obtain funding from additional sources to support its personnel and infrastructure. This resulted in up to $1 million from industry, $2 million from other federal institutions, and more than $7 million from other branches of the military in the early 2000s. It is not an overstatement to say that without ONR support the laboratory would not exist today. This support is particularly important in the current era as environmental laboratories are disappearing around the world. In 2008, ONR awarded CRESE a Defense University Research Instrument Program award, which allowed the complete refurbishment of the hyper/hypobaric chamber and purchase of modern measurement instrumentation. ONR also contributed funds to conduct an international symposium in Buffalo focusing on critical issues in undersea medicine. The proceedings from that symposium were published in a special issue of the Journal of Applied Physiology.

Another important aspect of ONR funding is the support for training future generations of scientists in environmental physiology and hyperbaric medicine. Over the years, ONR has routinely supported postdoctoral fellows who trained in CRESE. Several CRESE alumni assumed leadership positions in universities and in the Navy. Notable examples are Capt. James Vorosmarti, Capt. Edward Flynn, and Capt. Edward Thallman, who were all leaders in undersea medicine. In addition, CRESE has trained more than 100 undergraduate students, 98 graduate students, 20 medical students, 30 summer fellows, 32 postdoctoral fellows, and 24 distinguished visiting scientists from 15 different nations.

In spite of its success, CRESE met the fate of many other environmental physiology labs in 2013 when it was closed by the School of Medicine in anticipation of moving to a new downtown campus. Fortunately, this coincided with the arrival of the Emergency Responder Human Performance Lab (ERHPL) in the Department of Exercise and Nutrition Sciences. ERHPL had a similar environmental physiology focus for first responders and was able to acquire a portion of the CRESE infrastructure. Two years later, with the support of the Deans of Medicine, and the School of Public Health and Health Professions, CRESE reopened and ERHPL became one of three labs operating within the center.

However, after two years of sitting idle, much of the equipment, including the hyperbaric chamber, was in poor repair. Once again, ONR was instrumental in CRESE’s success. A Defense University Research Instrument Program grant was awarded, which allowed the university to rehabilitate the hyper/hypobaric chamber and to purchase equipment for data collection. Further research support was provided by ONR and Dr. William D’Angelo. Once again, this early support from ONR allowed CRESE to apply for grants from Naval Sea Systems Command and operate a fully functioning research and training program. Currently, CRESE is led by Dr. David Hostler (also director of ERHPL) and supports two additional researchers; Dr. Blair Johnson (director of the Human Integrative Physiology Lab) and Dr. Zachary Schlader (director of the Thermal Physiology Lab). All three are supported by ONR or Naval Sea Systems Command and contributing to the National Naval Responsibility Initiative.

Important Projects

CRESE was built on a legacy that began at the University of Rochester. Fenn, Rahn, and Ottis were recruited by the military to perform basic science studies to address military-relevant questions during World War II. Their work determined the supplemental O2 requirements to fly at higher altitudes in unpressurized aircraft and the hydration requirements for soldiers fighting in the African deserts. Rahn’s move to the University at Buffalo and the refocusing of the department on environmental issues in humans and animals led to the development of the laboratory, which was later named for him and eventually officially recognized as CRESE.

There were two initial areas of interest after establishing the environmental focus of the laboratory. The first was studies focused on breath-hold diving, including alveolar gas exchange and end-tidal gas measurement. The second was field studies describing the diving pattern, breath-holding capacity, and thermal stress of Ama divers (Japanese pearl divers). These studies set the stage for laboratory studies in the hyperbaric chamber, including simulated breath-hold diving to 50 meters to describe the cardiovascular changes, alveolar gas composition, CO2 storage capacity, and ventilatory responses to hypercapnia (elevated CO2 levels) and hypoxia in elite breath-hold divers. Another early focus was on deep sea diving. In the 1960s, prior to remotely operated vehicles, deep diving was of critical interest to both commercial and military communities. Studies were conducted on mice and humans examining pulmonary gas exchange when ventilated with oxygenated liquid. Other ONR-supported studies allowed the design and construction of “mini hyperbaric chambers” that allowed measurements on single living cells at elevated pressure.

In recent years, CRESE studies have focused on the mechanics of breathing, work of breathing, and ventilation-perfusion relationships using both theoretical and experimental methods. We have examined the effects of gas density during submersion and the effect of depth, static lung load, and posture on the heart and lungs at depth. Work performed at CRESE on the dead space in breathing apparatus contributed to the acceptable breathing resistance standards in working divers. The effects of the increased work of breathing and carbon dioxide retention have been a major focus of the laboratory.

Recently, ONR-supported studies that have quantified the effect of both submersion and depth on the work of breathing as well as the energy cost of breathing. These studies showed that improving respiratory muscle strength and endurance by respiratory muscle training reduces the work of breathing and the energy cost of respiration at depth. Those improvements in respiratory function increased exercise endurance on land and at depth making warfighters more effective.

The unique infrastructure allowed CRESE investigators to develop animal and human models to challenge the long- standing “Gauer-Henry” hypothesis of the link between the cardiovascular and renal systems. These studies collectively established the concept of autoinfusion of fluid from the cells to the intravascular compartment during immersion, which increases plasma volume. This, combined with hydrostatic pressure, results in translocation of fluid to the chest, increased stroke volume, and greater cardiac output. The presence of both expanded plasma volume and hormonal changes results in the immersion diuresis and eventually a reduction in plasma volume. These studies led to the questioning of rehydration during immersion and one of the current studies being performed in CRESE.

CRESE also is known for its ONR-supported work on diver thermal protection. Theoretical models and experimental data have documented the heat transfer in water of different temperatures at rest and during exercise. More recently, we have shown the effect of body cooling on oxygen transport during exercise, including reductions in cardiac output and skeletal muscle blood flow. The reduction in subcutaneous and muscle blood flow act as insulation during cold water diving. With the recognition of unsolved cold stress issues and the emergence of warm water issues, a second international symposium was held at CRESE to examine new technologies and strategies for thermal protection. ONR supported CRESE to develop a diver thermal protection system for use in both cold and warm water. A system was developed that could protect divers in water at 5 to 40 degrees Celsius down to a depth of 300 feet sea water, and served as a regional and total body calorimeter providing data for the power requirements to maintain diver thermal comfort. This system was transferred to NEDU for further exploration.

Current Projects

CRESE continues to advance the basic and applied science of diving. A current ONR-supported project entitled “The role of oxygen breathing on carotid body sensitivity, oxygen toxicity, and performance in divers” is ongoing. The research will determine if carotid body chemosensitivity is altered during and following a dive and if breathing 100-percent oxygen during a dive alters carotid body chemosensitivity when compared to breathing 21-percent oxygen.

Dr. Blair Johnson was awarded the ONR Director of Research Early Career Grant for his project entitled “Autonomic Activity and Water Immersion.” This study will investigate the changes in direct recordings of sympathetic nerve activity during various conditions associated with diving (thermoneutral water, cold water, breathing hyperoxia, breathing hypercapnia). These studies will provide important insights regarding the control of ventilation and circulation during water immersion. Naval Sea Systems Command continues to use CRESE resources to enhance diver safety and performance and is currently funding three projects. The first is entitled “Optimizing performance during topside operations at altitude.” There is little information available on the decompression stress of divers working at altitude. This proposal will examine the effects of respiratory muscle training on performance during topside operations and during diving at altitude. It also will explore the decompression strain that occurs after diving at altitude by assessing venous gas bubbling after diving at 12,000 feet of altitude.

Additional ongoing projects include examining rehydration strategies for Navy divers and special warfare operators exposed to prolonged immersion, who then proceed to land exercises, and the physiologic strain associated with prolonged exposure in a disabled submarine using a pressurized rescue module (PRM). Safe deployment of the PRM is dependent on understanding and mitigating the possible challenges if failures were to occur. If the PRM were to become disabled, the environmental conditions could quickly challenge the health and safety of those inside. There are no models capable of accurately predicting these variables in a hyperbaric, humid, and warm environment. This study will determine the magnitude of increases in core body temperature or reductions in body fluids incurred in a warm and humid disabled PRM scenario at sea level and at depth.

Historically, CRESE’s research has focused on the performance and safety of Navy personnel. Now positioned in the Department of Exercise and Nutrition Sciences, CRESE has additional expertise to renew that focus to explore and improve human performance in extreme environments—including new physical training paradigms, nutrition, thermal protection, and decompression strain with the aim of addressing field conditions using scientific techniques and methods.

About the authors:

Dr. Hostler is professor and chair with the Department of Exercise and Nutrition Sciences, and is director of the Center for Research and Education in Special Environments, at the State University of New York at Buffalo. Dr. Pendergast is professor emeritus of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences at the State University of New York at Buffalo.