An improved pre-clinical model of sepsis incorporating vasopressor support

A new article was recently published that I participated in during my time at NIH. The study was led by Tetsushi Yamashita and focuses on changes in blood pressure and heart rate during sepsis. Unlike previous articles that focused on the pathways involved in the progression of sepsis this study examined some of the treatment options that are typically used in patients.

Although this study built on our knowledge of the complex response to sepsis it also developed an existing mouse model of sepsis closer to what humans might experience during routine care. The more accurately our models can simulate human disease the more likely we are to successfully translate therapies from mice into humans.

Mice are widely used as models of disease including kidney disease and sepsis despite differences between these mouse models and humans. There are a variety of reasons for these differences with medical care being one we can reduce.

When sepsis is diagnosed common medical treatments include giving fluids, antibiotics and vasopressors such as norepinephrine (also called noradrenaline in the UK) to treat low blood pressure. Each of these treatments alter disease progression in humans but are relatively new developments in mouse models. Our lab had a long history of using fluids and antibiotics but vasopressors were not used.

The reason for this is simple: their use is technically very challenging. While fluids and antibiotics can be administered intermittently and via common injection routes vasopressors would need to be administered:

  1. directly into a vein
  2. continuously
  3. and with careful monitoring

The experimental procedures necessary for this model were first brought together by Brianna Halasa and then finalised when Tetsushi joined the lab. Each mouse undergoes approximately one hour of surgery in which the jugular vein is catheterised to enable the infusion of a vasopressor and then the carotid artery is catheterised to implant a pressure transducer to monitor blood pressure. Although the exact procedures are slightly different these videos demonstrate the jugular vein and carotid artery catheterisations. Only when the mice have recovered does the more usual sepsis model surgeries begin.

I would like to congratulate Tetsushi on publishing this study. If you are interested in learning more the complete article is now freely available in PLoS One.