1. The Development of a Translational Model for the Analysis of Microvascular Failure in Sepsis March 26, 2013 Rachel McInnis Department of Medical Biophysics Schulich School of Medicine & Dentistry Western University Supervisor: Dr. Chris Ellis Department of Medical Biophysics

2. What is sepsis? Sepsis is an excessive inflammatory response due to bacterial infection: peritonitis pneumonia urinary tract infection It is characterized by multiple system organ failure

3. Motivation In a prospective study of Canadian intensive care units 19% of all intensive care patients had severe sepsis Patients diagnosed with severe sepsis had a 38.1% hospital mortality rate Over 70 clinical trials have failed to develop a treatment to reduce patient mortality

4. Methods

5. Three groups: 1. Sham (control) where the surgical procedure is performed, but sepsis is not induced 2. Induce sepsis using a fecal injection into the peritoneum (FIP) 3. 3 hours after inducing sepsis fluid resuscitation is initiated by increasing saline to a rate of 2.5 ml/hr Observe the microcirculation using a dual wavelength video microscopy system 5 minute videos x 1 field of view every hour

6. Methods

8. Sham - One Hour

9. Sham - Three Hours

10. Sham - Five Hours

11. Septic - One Hour

12. Septic - Three Hours

13. Septic - Four Hours

14. Fluid-resuscitated Sepsis Model- Five Hours

15. Fluid-resuscitated Sepsis Model- Ten Hours

16. Conclusions This method enables the observation of microvasculature remote to initial site of injection Sepsis results in microvasculature dysfunction; however, fluid resuscitation has been shown to improve capillary perfusion Future Work Complete quantitative analysis using functional capillary density Focus on the development of a clinically relevant model of sepsis

17. Acknowledgements Dr. Chris Ellis Nathaniel Hayward Stephanie Milkovich

18. Questions