5.1. Possible organ protective effects of hexafluoroisopropanol (HFIP) in a model
of myocardial infarction
Coronary heart disease is one of the major causes of death in the western civilization. To reduce the ischemic injury due to atherosclerotic plaque formation of the infarcted heart, the treatment of choice is the timely reperfusion of the infarcted, non-perfused area. However, reperfusion of the infarcted myocardial tissue itself leads to a subsequent ischemia-reperfusion injury. An option to reduce the ischemia-reperfusion-induced inflammatory response would be the use of volatile anaesthetics upon reperfusion. While this is possible during the invasive procedure of coronary artery bypass graft surgery as the patients are under anaesthesia, interventions such as placement of intracoronary stents do not allow application of volatile anaesthetics as there is no need for a general anaesthesia.
Our research group has recently shown the immunomodulatory potential of hexafluoroisopropanol (HFIP) in severe systemic inflammation. HFIP is a water-soluble metabolite of sevoflurane, consisting of trifluorinated carbon groups. In this current study we will evaluate the effect of HFIP application on inflammation and remodelling processes in a model of myocardial ischemia-reperfusion injury.
5.2. Hexafluoroisopropanol (HFIP): bringing a drug from preclinical to clinical testing
Unitectra, Technology Transfer, University of Zurich
As previously shown hexafluoroisopropanol (HFIP) attenuates severe inflammatory processes such as sepsis both in vitro and in vivo. This metabolite of the volatile anesthetic sevoflurane is water-soluble, which would allow an intravenous infusion. Moreover when using HFIP an anaesthetic effect is missing. Therefore the application would not be restricted to controlled environments such as operating theaters or intensive care units.
In an acute as well as in a chronic phase of sepsis this water-soluble sevoflurane metabolite decreased systemic inflammation, but also positively impacted on the inflammatory orchestration in various organs such as liver, lung and kidney. Moreover, HFIP improved survival rate in a sepsis model from 20% to 80%. As a further consequence in the development of this drug further in vivo studies will be performed, which should finally allow drafting a first phase I trial.
Urner M, Schläpfer M, Herrmann IK, Hasler M, Schimmer RR, Booy C, Roth Z'graggen B, Rehrauer H, Aigner F, Minshall RD, Stark WJ, Beck-Schimmer B
Insight into the beneficial immunomodulatory mechanism of the sevoflurane metabolite hexafluoro-2-propanol in a rat model of endotoxaemia
Clin Exp Immunol, 2015; 181(3):468-79c
Herrmann IK, Castellon M, Schwartz DE, Hasler M, Urner M, Hu G, Minshall RD, Beck-Schimmer B
Intravenous application of a primary sevoflurane metabolite improves outcome in murine septic peritonitis: first results
PLoS One, 2013; 8(8):e72057