Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

Research Interests:

-Regulation of nitric oxide synthesis.
-Intermittent hypoxia as an inflammatory stimulus.
-Acute lung injury

Keywords:

Nitric oxide, cell culture, macrophages, endothelial cells, cardiac myoctyes, drosophila, acute lung injury, rabbits, inflammation, gene expression.

Research Summary:

The effects of intermittent hypoxia on regulation of inflammatory mediators.
This project uses stringently controlled oxygen tensions and real time NO measurments to investigate the mechanism by which intermittent hypoxia alters inflammatory mediators. We are using several different models to evaluate the pathways involved in signaling. In vitro, we are predominantly studying macrophages, but have recently expanded to evaluate cardiac myocytes, endothelial cells and respiratory epithelial cells. We are currently investigating the effect of 1) high frequency intermittent hypoxia (such as is seen in some cases of acute respiratory distress syndrome), 2) moderate frequency intermittent hypoxia (such as is seen with obstructive sleep apnea) and 3) sustained hypoxia. Our overall objective is to identify the mechanisms by which oxygen regulates nitric oxide and other inflammatory mediator production.

In our whole animal investigation of intermittent hypoxia, we study a saline lavage model of acute lung injury in rabbits, we have identified marked oscillations in arterial oxygen tension with every breath (high frequency intermittent hypoxia). We have demonstrated that these oscillations are associated with an inflammatory response in the lungs of the rabbits.

In drosophila, we have developed a system to deliver intermittent hypoxia to flies. We have investigated the effects of this form of oxidative stress on longevity and are currently evaluating a series of flies with mutations in different inflammatory pathways.


Possible Lab Rotation Projects:

-Determine the critical arginine concentration for NO production under normoxic and hypoxic conditions.

- Determine the critical frequency, amplitude and duration of intermittent hypoxia to trigger NF-kB, NO production and inflammatory mediators in cultured macrophages.

-Determine the effect of media from macrophages cultured under hypoxia and intermittent hypoxia on cardiac myocyte function and viability.

-Determine the effect of media from macrophages cultured under hypoxia and intermittent hypoxia on endothelial function and inflammatory response.

- Determine the critical frequency, amplitude and duration of intermittent hypoxia to trigger inflammation in cultured endothelial cells.

-Determine the critical frequency, amplitude and duration of intermittent hypoxia to trigger inflammation in cultured cardiac myocytes.

- Evaluate the relative effect of intermittent hypoxia on oxidative stress, inflammation and survival in drosophila.

Description of Clinical Expertise

Board certified in veterinary emergency and critical care, my main clinical responsibility is as an attending in the veterinary emergency service at the Ryan veterinary hospital. My primary clinical research interests encompass naturally occurring animal diseases as models of human and animal disease with an emphasis on inflammation, sepsis and trauma. I am also a member of the Veterinary Clinical Investigation Center, the primary resource for conducting veterinary clinical trials at the University of Pennsylvania.

Selected Publications

Robinson, MA, Baumgardner, JE, Good, VP, Otto, CM: Physiological and hypoxic O-2 tensions rapidly regulate NO production by stimulated macrophages American Journal Of Physiology-cell Physiology 294(4): C1079-C1087, APR 2008.

Otto, CM, Markstaller, K, Kajikawa, O, Karmrodt, J, Syring, RS, Pfeiffer, B, Good, VP, Frevert, CW, Baumgardner, JE: Spatial and temporal heterogeneity of ventilator-associated lung injury after surfactant depletion Journal Of Applied Physiology 104(5): 1485-1494, MAY 2008.

Otto CM : Clinical Trials in Spontaneous Disease in Dogs: A New Paradigm for Investigations of Sepsis. J Vet Emerg Crit Care 17(4):359-367, 2007. 17(4): 359-367, Dec 2007.

Alwood, AJ, Downend, AB, Brooks, MB, Slensky, KA, Fox, JA, Simpson, SA, Waddell, LS, Baumgardner, JE, Otto, CM: Anticoagulant effects of low-molecular-weight heparins in healthy cats Journal Of Veterinary Internal Medicine 21(3): 378-387, MAY-JUN 2007.

Syring, RS, Otto, CM, Spivack, RE, Markstaller, K, Baumgardner, JE: Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury Journal Of Applied Physiology 102(1): 331-339, JAN 2007.

Pfeiffer, Birgit. Syring, Rebecca S. Markstaller, Klaus. Otto, Cynthia M. Baumgardner, James E.: The implications of arterial Po2 oscillations for conventional arterial blood gas analysis. Anesthesia & Analgesia 102(6): 1758-64, Jun 2006.

Otto, CM, Downend, AB, Serpell, JA, Ziemer, LS, Saunders, HM: Medical and behavioral surveillance of dogs deployed to the World Trade Center and the Pentagon from October 2001 to June 2002 Journal Of The American Veterinary Medical Association 225(6): 861-867, SEP 15 2004.

Slensky, KA, Drobatz, KJ, Downend, AB, Otto, CM: Deployment morbidity among search-and-rescue dogs used after the September 11, 2001, terrorist attacks Journal Of The American Veterinary Medical Association 225(6): 868-873, SEP 15 2004.

Baumgardner, JE, Otto, CM: In vitro intermittent hypoxia: challenges for creating hypoxia in cell culture Respiratory Physiology & Neurobiology 136(2-3): 131-139, JUL 16 2003.

Baumgardner, JE, Markstaller, K, Pfeiffer, B, Doebrich, M, Otto, CM: Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on Pa-o2 oscillations after saline lavage American Journal Of Respiratory And Critical Care Medicine 166(12): 1556-1562, DEC 15 2002.