From the Lab
From Mountain High to Valley Low Exploring New Scientific Frontiers with the Duke Human Pharmacology and Physiology Lab By David B. MacLeod, MB, BS, FRCA, and Lauren Marcilliat
The HPPL is housed within the Duke Clinical Research Unit (DCRU) and does a combination of anesthesia-related equipment, pharmacology, and human physiology studies on healthy human subjects. Experiments are conducted in (Left to Right) The HPPL team: Antoinette Santoro, BSRT, a controlled setting with David B. MacLeod, MB BS, FRCA, and Daniel DeMasi. extensive physiological monitoring and without the confounding issues of surgery and anesthesia. These studies are important because they provide insight into the mechanisms of human pathophysiology and help identify new drugs and technology with the potential to improve patient outcomes. The HPPL team is comprised of Director, David B. MacLeod, MB BS, FRCA, Clinical Research Coordinator, Antoinette Santoro, BSRT, and Clinical Trial Assistant, Daniel DeMasi. Additionally, Duke Anesthesiology attending physicians and CRNAs help to run studies on an as-needed basis. HPPL staff work closely with the Duke Institutional Review Board (IRB) to ensure the safety and well-being of their subjects. “Every study is meticulously planned and executed,” says Dr. MacLeod. “Working with healthy subjects is challenging because they must 34
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trust you explicitly while they receive no medical benefit from the study. In my ten years as director, I am proud to say that we have safely conducted every one of the studies with no serious adverse events, totaling over 600 human subjects.” The Human Pharmacology Lab (HPL as it was originally called) initially focused exclusively on pharmacokinetics and was established in the mid-1980s by Professor Peter Glass. Here, he made several important advances in anesthesia care, such as the initial studies on BIS monitor and the concept of context-sensitive halftimes of intravenous anesthetics and analgesics. In 1999, Jacques Somma, MD, took over the lab, and began a collaboration with Dr. MacLeod, who was a new faculty member at the time. Under Dr. Somma’s direction, Dr. MacLeod quickly gained expertise in conducting Phase I studies and found that he thrived in the unique environment that the HPL offered. When Dr. Somma left Duke in 2006, Dr. MacLeod took over as director. Under Dr. MacLeod’s leadership, the HPL lab expanded its focus and scope of work to become the HPPL lab. The following three studies serve as examples of how the HPPL lab has grown both at home and abroad under Dr. MacLeod’s directorship:
Hypoxia Studies at the Pyramid Lab
Dr. MacLeod’s experience in the placement jugular bulb venous catheters and controlled oxygen desaturation as part of cerebral oximeter validation studies to estimate brain tissue oxygen saturation led to an initial collaboration with the University of British Columbia, Okanagan (UBCO), Canada to study cerebral blood flow (CBF) during hypoxia in 2011. The team studied changes in regional cerebrovascular response to acute changes in blood gases with use of a Transcranial Doppler (TCD) to measure intracranial velocities of middle and posterior cerebral arteries and the simultaneous use of Duplex vascular ultrasound to measure the extracranial blood flow of the internal Arterial catheter placement at 5050m in the Pyramid Lab carotid and vertebral (Nepal) with the Lobuche Glacier in the background.
Photos and Figures Courtesy of Dr. David B. MacLeod
To work at the Duke Anesthesiology Human Pharmacology and Physiology Lab (HPPL), one must exhibit equal competence in both the clinical and research setting and the ability to seamlessly transition between the two. A passion for discovery, strong people skills, and a healthy dose of wanderlust certainly don’t hurt either.
DUKE ANESTHESIOLOGY
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