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Anesthesiology:
doi: 10.1097/01.anes.0000279486.77183.65
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Marcos F. Vidal Melo, M.D., Ph.D., Recipient of the 2007 Presidential Scholar Award

Zapol, Warren M. M.D.*

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DURING the past 50 yr, anesthesiologists have been leaders in forging practical advances in the care of patients with severe respiratory failure. Perhaps the foremost contribution was the development of tracheal intubation and mechanical ventilation, the latter led by Scandinavian anesthesiologists responding to the polio epidemics of the 1950s. This advanced respiratory care from the use of clumsy, complex, inconvenient iron lungs to mechanical ventilation with enhanced respiratory patterns, including the use of positive end-expiratory pressure to reverse lung collapse and maintain the lung's end-expiratory gas volume. Other advances by anesthesiologists included the invention of the carbon dioxide electrode, which allowed arterial carbon dioxide tension measurements; the development of respiratory care units to collect and treat surgical patients; and therapeutic innovations such as inhaled nitric oxide to control the distribution of pulmonary blood flow when the inflamed lung fills with fluid and cells and the natural process of alveolar ventilation to perfusion (V̇ A/Q̇) matching fails to maintain a safe arterial oxygen tension. Several of these advances were made by immigrants to the United States (Henning Pontoppidan, M.D., Henrik H. Bendixen, M.D. [December 2, 1923–April 4, 2004], Myron B. Laver, M.D. [August 17, 1926–August 31, 1982], and John Hedley-White, M.D.) who, as it happens, worked in the laboratories, operating rooms, and intensive care units of the Massachusetts General Hospital (Boston) Department of Anesthesia (now the Massachusetts General Hospital Department of Anesthesia and Critical Care). The recipient of the American Society of Anesthesiologists 2007 Presidential Scholar Award, Dr. Marcos F. Vidal Melo, continues this tradition.
Dr. Vidal Melo is a native of São Gonçalo near Rio de Janeiro, Brazil. He obtained an early exposure to many professions and a love for learning from his parents. His father was a graduate in accounting, economy, and law, and his mother was a schoolteacher who supervised a backyard school during his early childhood. There, under her guidance, Dr. Vidal Melo learned his ABCs and math facts. His parents taught him by example, especially regarding the importance of dedication, resourcefulness, and determination. Dr. Vidal Melo is the oldest of three siblings; his brother is a lawyer, and his sister is a psychologist who also teaches English. With his wife, Monica Sa Rego, an anesthesiologist at the Brigham and Women's Hospital in Boston, he shares a fondness for nature, traveling, and music, and the loving care of their son Vinicius, a junior in high school.
Dr. Vidal Melo began his career in Brazil, developing a keen interest in the integration of engineering and medicine. He received a B.Sc. in Civil Engineering and an M.Sc. in Biomedical Engineering from the Federal University of Rio de Janeiro (Brazil), and later an M.D. from the Fluminense Federal University (Niterói, Brazil). His focus on combining pulmonary gas exchange and mathematical modeling commenced when he did a rotation in Anesthesiology at the Medical School and, at the same time, research in Pulmonary Bioengineering under Prof. A. Giannella Neto in his M.Sc. program. Dr. Vidal Melo pursued this combination of interests in his doctorate in Experimental Surgery at the University of Heidelberg, Germany, with Prof. Konrad Messmer as his adviser. In Heidelberg, he developed predictors of outcome in the acute respiratory distress syndrome based on cardiopulmonary variables.
In 1995, he emigrated to the United States to commence a clinical anesthesiology residency at Southwestern Medical Center, Dallas, Texas, and then in 1998, his interest in acute respiratory distress syndrome and research motivated him to complete his residency and a cardiac anesthesia fellowship in the Department of Anesthesia and Critical Care at Massachusetts General Hospital. After completing his four programs of advanced degree training in 2000, Dr. Vidal Melo joined a world-famous bioengineer, Jose Venegas, Ph.D., and his team to study the lung's function using positron emission tomography (PET). For the past 6 yr, Dr. Vidal Melo has focused his research efforts on the advancement of PET-based techniques to study ventilation, perfusion, and inflammation in the lung, and he has applied these techniques to patients with lung disease and to animal models of lung disease. The complexity of these collaborative studies, requiring teamwork from a group of engineers, physicians, physiologists, physicists, and biochemists, makes them quintessentially multidisciplinary efforts, the results of which are attributable to all. Therefore, in the description of the scholarly development of Dr. Vidal Melo's studies that follows, all must be acknowledged as having played a vital role.
Modern imaging techniques provide superb topographical information at high resolution about many organs and tissues of the body. However, lung imaging has lagged behind the advances in imaging of other organ systems, thereby slowing the rate of improvement in our understanding, diagnosis, and treatment of pulmonary diseases. For example, until recently, imaging techniques provided only qualitative information regarding gas exchange, i.e., imaging data could not be translated into function, such as quantifying the arterial blood oxygen tensions produced by heterogeneously diseased lungs. With his colleague Dr. Venegas, Dr. Vidal Melo designed a novel method to estimate V̇ A/Q̇ distributions from the elimination kinetics of the cyclotron produced radioactive tracer 13N,1 and he demonstrated that arterial blood oxygen tensions could be accurately predicted based primarily on PET measurements. This was the first time an imaging technique allowed the accurate quantification and prediction of pulmonary gas exchange, and it is the only method capable of doing so in highly heterogeneously diseased human lungs. Other insights into the dysfunction of the human lung followed; Dr. Vidal Melo learned that significant V̇ A/Q̇ heterogeneity was present in very small lung regions, corresponding to a single imaging unit (a pixel). As in so many of his studies, his unique combination of bioengineering and physiology skills brought important new concepts to the field of lung injury.
Recent work by Dr. Vidal Melo and his colleagues has provided us with insights into the topographical basis of the V̇ A/Q̇ mismatching and hypoxemia that accompanies acute bronchoconstriction in asthmatics. It was known that the V̇ A/Q̇ mismatching occurring during acute bronchoconstriction is not random, but rather demonstrates a bimodal distribution, i.e., V̇ A/Q̇ ratios in those lungs are either near normal or very low with few intermediate values. However, the topographical or anatomical basis for this phenomenon was unknown. Dr. Vidal Melo produced an experimental model of bronchoconstriction with his colleague R. Scott Harris, M.D. (Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA) and demonstrated that a significant portion of the V̇ A/Q̇ bimodality was present in very small regions of the lung,2 smaller than secondary pulmonary lobules (2.2 cm3), although classic chest radiographs misleadingly showed large regions of lung collapse and reduced ventilation. Laboratory studies by Dr. Vidal Melo and his colleagues3 indicated that V̇ A/Q̇ heterogeneity after pharmacologically triggered bronchoconstriction was correlated with the degree of preexisting heterogeneity, suggesting that improving the uniformity of ventilation was the desired therapeutic target. In summary, Dr. Vidal Melo and his coworkers have advanced our structural and functional understandings of the lung, and this allowed them to propose an exciting new model (using chaos theory) to explain the effects of bronchoconstriction in humans.4
Pulmonary inflammation both results from and causes lung dysfunction. Recently, Dr. Vidal Melo has been funded by the National Heart, Lung, and Blood Institute (Bethesda, MD) to work with Guido Musch, M.D., Tilo Winkler, Ph.D., and Tobias Schroeder, M.Eng. (Research Fellow) (all with the Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA) and develop methods for topographically assessing regional inflammation with PET, and combining these results with physiologic analyses to examine regional function in the lung. Their investigations of both smoke inhalation and ventilator-induced lung injury have shown the ability of PET techniques to detect and quantify regional neutrophil infiltration in these forms of lung injury, the significance of lung expansion on the magnitude and distribution of inflammation during mechanical ventilation,5 and the importance of preexisting V̇ A/Q̇ heterogeneity to regional inflammation after smoke inhalation.6 Upcoming studies are expected to bring us novel insights into the inflammatory mechanisms of ventilator-induced lung injury occurring in human lungs.
Positron emission tomography methods have provided important insights into other conditions leading to lung dysfunction. Investigating pulmonary embolism, Dr. Vidal Melo and his collaborators developed an experimental model of massive pulmonary embolism.7 They showed in vivo that adaptive changes of pulmonary ventilation occur soon after pulmonary embolism and result in shifting of regional ventilation from embolized to nonembolized areas. In acute lung injury, they have shown that the fraction of available gas volume participating in gas exchange undergoes a greater reduction in the supine as compared with the prone position,8 supporting use of prone positioning in intensive care unit patients with adult respiratory distress syndrome. Importantly, they discovered that gas exchanging pulmonary air volume was substantially less than the total air volume of the lungs. This implies that the significant impairment in the distribution of regional alveolar volume to perfusion that occurs after acute lung injury is superimposed on the dysfunction caused by pulmonary edema, and can be altered by mechanical ventilation and posture to optimize gas exchange.
In addition to his pulmonary imaging studies, Dr. Vidal Melo serves as our Director of Research in Cardiac Anesthesia, and he has led a number of investigator-initiated and industry-sponsored clinical studies at the Massachusetts General Hospital. This has given our residents and fellows the opportunity to participate in clinical investigation and has attracted physicians from other countries to their group. Dr. Vidal Melo has been awarded funding from the Society of Cardiovascular Anesthesiologists (Richmond, VA) as well as the pharmaceutical industry for his innovative studies of perioperative organ dysfunction during and after cardiac surgery.
Dr. Vidal Melo is respected and esteemed by our staff as a skillful clinician and coworker. Residents and fellows consider him an excellent teacher, and frequently comment on his ability to fuse basic scientific knowledge with daily clinical practice, bringing his intellectual depth and pervasive curiosity to the teaching and practice of anesthesiology.
Figure. Marcos F. Vi...
Figure. Marcos F. Vi...
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In summary, Marcos F. Vidal Melo typifies the innovative clinician–scientist that we seek to develop in our educational programs and attract to our medical specialty. He has contributed to developing and implementing modern lung imaging techniques that help us to better understand severe lung dysfunction in several diseases. He is an important leader of an emerging, important field of research. Dr. Vidal Melo is poised to improve our care of the respiratory failure patient by giving us a better understanding of the dysfunction of the injured lung. He is a most deserving recipient of the American Society of Anesthesiologists 2007 Presidential Scholar Award.
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References

1. Vidal Melo MF, Layfield D, Harris RS, O'Neill K, Musch G, Richter T, Winkler T, Fischman AJ, Venegas JG: Quantification of regional ventilation-perfusion ratios with PET. J Nucl Med 2003; 44:1982–91

2. Vidal Melo MF, Harris RS, Layfield JD, Venegas JG: Topographic basis of bimodal ventilation-perfusion distributions during bronchoconstriction in sheep. Am J Respir Crit Care Med 2005; 171:714–21

3. Venegas JG, Schroeder T, Harris S, Winkler RT, Vidal Melo MF: The distribution of ventilation during bronchoconstriction is patchy and bimodal: A PET imaging study. Respir Physiol Neurobiol 2005; 148:57–64

4. Venegas JG, Winkler T, Musch G, Vidal Melo MF, Layfield D, Tgavalekos N, Fischman AJ, Callahan RJ, Bellani G, Harris RS: Self-organized patchiness in asthma as a prelude to catastrophic shifts. Nature 2005; 434:777–82

5. Musch G, Venegas JG, Bellani G, Winkler T, Schroeder T, Petersen B, Harris RS, Vidal Melo MF: Regional gas exchange and cellular metabolic activity in ventilator-induced lung injury. Anesthesiology 2007; 106:723–35

6. Schroeder T, Vidal Melo MF, Musch G, Harris RS, Winkler T, Venegas JG: PET imaging of regional 18F-FDG uptake and lung function after cigarette smoke inhalation. J Nucl Med 2007; 48:413–9

7. Vidal Melo MF, Harris RS, Layfield D, Musch G, Venegas JG: Changes in regional ventilation after autologous blood clot pulmonary embolism. Anesthesiology 2002; 97:671–81

8. O'Neill K, Venegas JG, Richter T, Harris RS, Layfield JD, Musch G, Winkler T, Vidal Melo MF: Modeling kinetics of infused 13NN-saline in acute lung injury. J Appl Physiol 2003; 95:2471–84

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