The proposed research titled The impact of anesthetic selection on sepsis outcome and its mechanism is to study the impact of daily used anesthetic drugs on sepsis pathophysiology. Despite extensive research on sepsis pathophysiology, and initiation of protocol-driven sepsis management worldwide, the mortalities of sepsis continue to be high at around 20-30%. One of the cardinal tenets of sepsis management is infection source control. Patients suffering from sepsis, particularly abdominal sepsis often undergo source control procedures under general anesthesia on an emergent or urgent basis. Pediatric patients often require general anesthesia even for imaging studies to identify the source of infection. Despite the reports of potential effects of anesthetics on immune functions in vitro, there is a paucity of research investigating the in vivo significance and underlying mechanisms. We previously reported that the commonly used anesthetics isoflurane, sevoflurane and propofol differently affected critical adhesion molecules LFA-1 and Mac-1 on immune cells in vitro. In this project we hypothesize that these anesthetics have different impacts on sepsis outcome via their differential effects on LFA-1 and Mac-1. To test this hypothesis, we will perform the study of the three common anesthetic drugs isoflurane, sevoflurane and propofol, using polymicrobial abdominal sepsis model in mice.
In Aim 1, we will determine the role of LFA-1 and Mac-1 and the impact of anesthetics in neutrophil recruitment.
In Aim 2, we will determine the role of LFA-1 and Mac-1 and the impact of anesthetics in neutrophil bacterial phagocytosis.
In Aim 3, we will determine the impact of these anesthetics on outcome, systemic bacterial loads and systemic tissue injury. In addition, we will evaluate if anesthetics affect bacterial profiles and growth directly. The characterization of immunological impact by anesthetics in our proposed study will provide the in- depth insight of anesthetic effects on sepsis pathophysiology and lead anesthesia providers to reconsider how to anesthetize patients suffering from sepsis.
Volatile anesthetics have been given to patients for more than 150 years to provide general anesthesia, but the mechanism of their anesthetic actions is yet to be determined. Our previous data suggest that these drugs interact with adhesion molecules on immune cells and affect their functions. The proposed study is 1) to address the impact of different anesthetics on neutrophils, the first defense cells in our immune system and 2) to study the effect of different anesthetics on the outcome of sepsis, severe type of infection in mice.
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| Okuno, Toshiaki; Koutsogiannaki, Sophia; Ohba, Mai et al. (2017) Intravenous anesthetic propofol binds to 5-lipoxygenase and attenuates leukotriene B4 production. FASEB J 31:1584-1594 |
| Chamberlain, Matthew; Koutsogiannaki, Sophia; Schaefers, Matthew et al. (2017) The Differential Effects of Anesthetics on Bacterial Behaviors. PLoS One 12:e0170089 |
| Yuki, Koichi; Eckenhoff, Roderic G (2016) Mechanisms of the Immunological Effects of Volatile Anesthetics: A Review. Anesth Analg 123:326-35 |
