Grant: Project Grant

Sepsis (ie. serious infections of the blood) can cause a vicious cycle of blood clot formation, inflammation, and cell death which may lead to blood clot formation, multiple organ failure, and even death. In Canada, there are approximately 90,000 patients with sepsis each year, with estimated mortality rates of up to 30%. Despite decades of sepsis research, there are no anti-sepsis drugs and the mortality rate of sepsis remains high. This suggests that some fundamental knowledge is lacking in our current understanding of why sepsis kills patients. Given the extensive biological crosstalk between infection, blood clotting, inflammation, and cell death, there has been renewed interest in heparin as a potential anti-sepsis therapy. Heparin is best know for its activities as a blood thinner. However, heparin can also dampen inflammation and prevent cell death during serious infections. Recent studies in COVID-related sepsis suggests that heparin can improve outcome in mildly ill patients but not in severely ill patients who require ICU care. Thus, we hypothesize that the beneficial effect of heparin may depend on the time of administration of heparin. In this study, we will use a mouse model of abdominal sepsis. We will identify the optimal time frame to administer heparin that will improve survival. We will study four different heparin variants which differ in their size and/or blood thinner activities. These studies may reveal if the protective effect of heparin requires its blood thinning activity and/or its large size. We will also study blood samples from patients with mild forms of sepsis to see if treatment with heparin will reduce blood clotting, inflammation, and cell death. Our research will improve our understanding of how heparin can improve outcome in patients with sepsis. This research has a direct pathway to implemental in clinical practice since heparins are inexpensive, widely available, and commonly used in medicine.