Andrew J. Lechner
Ph.D., University of California , Riverside , 1977, Physiology
Pharmacological & Physiological Science
Academic Rank: Professor
Phone: 314-977-6475 Fax: 314-977-6411
Lab Web Page Links:
Primary Area of Cardiovascular Research Interest
-Cardiopulmonary responses to compartmentalized sepsis and inflammation, notably so-called “two hit” models in which preexisting organ injury predisposes the host to a second insult.
-Interplay of heart and lung systems during use of mechanical ventilation
Related Areas of Cardiovascular Research Interest
-Oxygen transport physiology as applied to perinatal development
-Cardiopulmonary adaptations to exercise and high altitude
-Assessment of innovative pharmacological strategies to maximize organ system perfusion
Summary of Cardiovascular Research Interest
We are particularly interested in using robust in vivo and ex situ animal models of sepsis and inflammation to investigate novel approaches and therapeutics that extend life and prevent multiple systems organ failure. In just-completed studies, our group characterized distinct pathophysiological responses to variant strains of the plague bacterium Yersinia pestis as part of national research efforts against pathogens considered to have bioterrorist potential. Importantly, we showed that the progression from primary pneumonic infection to hepatic failure and fatal septic shock depended on expression of Yersinia outer proteins encoding a type III secretion apparatus whose gene products suppress host innate immunity.
Our collaborative effort with the NIH and a small biotechnology company demonstrated in this plague pneumonia model that a novel antagonist of the adenosine type 1 receptor (A 1 AR) significantly improved survival and liver function over the use of appropriate antibiotics alone. Our studies indicated that the vasoactive as well as immunomodulatory properties of this antagonist improved hepatic blood flow and clearance of xenobiotics, and the eradication of disseminated tissue infections. Indeed, the success of that study encouraged the NIH to seek our evaluation of that same A 1 AR antagonist in a different rodent model of compartmental polymicrobial sepsis initiated by cecal ligation and puncture. That work is currently underway.
In addition to using chronically instrumented rats, we employ isolated organ perfusion systems (lung, liver) and in vitro culture of both primary and established cell lines to provide a vertical approach to investigating such core issues within the broad area of critical care medicine.