Innate immunity and its influence on cardiovascular function

In Canada, severe infection, or sepsis, is the most common acute illness causing death. Patients with severe infections can go into shock as a result of progressive cardiac collapse and can die within 24 to 48 hours. The mortality rate of sepsis is 40%. The fact that this rate has not changed in the last 30 years illustrates that very little is known about how infection causes cardiovascular dysfunction and that very little is known about the best ways to prevent this from occurring.

Dr. John Boyd's research program is using a two-pronged approach to understand how sepsis causes progressive cardiac collapse. The objective of his clinical research program is to identify prognostic factors and to characterize the cardiac response to infection in patients with sepsis. Specifically, he is focusing on very early enrollment of acutely ill patients with infection presenting to the St. Paul's Hospital emergency department in order to identify prognostic factors such as new biomarkers and the presence of emerging infections. He will characterize their cardiovascular response to infection using a bedside cardiac ultrasound. Although previous work in this area has been done, patients were recruited from critical care units 24 to 36 hours following admission, too late to identify prognostic markers and intervene to improve outcome.

As a complementary approach, Dr. Boyd's pre-clinical (basic) research program is taking a molecular approach and using the immune system as a tool in the fight against cardiovascular collapse. He has identified a "counter-regulatory" receptor which appears able to reverse the heart damage induced by other receptors in the same family. The identification of this receptor will hopefully lead to the development of a targeted intervention for sepsis-related cardiovascular dysfunction. Dr. Boyd's clinical research program aims to answer simple but as-yet unstudied questions such as the optimal volume of IV fluid and how one can reliably diagnose infection. Although the results of his laboratory work are not yet close to reaching the bedside, they may potentially lead to therapies in the future.