The Development of a Translational Model for the Analysis of

Microvascular Failure in SepsisMarch 26, 2013

Rachel McInnisDepartment of Medical Biophysics

Schulich School of Medicine & DentistryWestern University

Supervisor: Dr. Chris Ellis

Department of Medical Biophysics

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

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

Methods

Methods• 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

Methods

Sham - One Hour

Sham - Three Hours

Sham - Five Hours

Septic - One Hour

Septic - Three Hours

Septic - Four Hours

Fluid-resuscitated Sepsis Model- Five Hours

Fluid-resuscitated Sepsis Model- Ten Hours

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

Acknowledgements• Dr. Chris Ellis

• Nathaniel Hayward

• Stephanie Milkovich

Questions