Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury: A Pilot Study in Healthy Volunteers
Status:
Completed
Trial end date:
2015-12-01
Target enrollment:
Participant gender:
Summary
Oxygen treatment is widely used in acutely ill patients. In particular, oxygen treatment is
routinely used in acute coronary syndrome (ACS) patients with suspected acute myocardial
infarction and variably recommended in ACS-guidelines, despite very limited data supporting a
beneficial effect.
Immediate re-opening of the acutely occluded infarct-related bloodvessel via primary
percutaneous coronary intervention (PCI) is the treatment of choice to limit ischemic injury
in the setting of ST-elevation ACS (STE-ACS). However, the sudden re-initiation of blood flow
achieved with primary PCI can give rise to further damage, so-called reperfusion injury.
Ischemia and reperfusion associated myocardial injury (IR-injury) involves a wide range of
pathological processes. Vascular leakage, activation of cell death programs, transcriptional
reprogramming, no reflow phenomenon and innate and adaptive immune activation all contribute
to tissue damage, thereby determining the infarct size. The effect of oxygen treatment on
these pathological processes, on the extent of IR-injury and the final infarct size in
STE-ACS patients has not previously been studied.
ACS is characterized by a systemic inflammation with typical elevations of soluble
inflammatory markers as well as changes in white blood cells. The inflammatory reaction might
be considered helpful in restoring myocardial tissue structure and function, but on the other
hand it might worsen IR-injury by activating various pathological processes. In human
experimental studies, Salmonella typhi vaccine has been used to create a standardized model
of systemic inflammation and when administered to healthy volunteers the vaccination has not
been associated with any adverse events.
In an ongoing register randomized multicentre clinical trial, the DETO2X (Determination of
role of oxygen in suspected acute myocardial infarction) study, the effect of oxygen on
morbidity and mortality in ACS patients is being investigated. In a substudy of the
DETO2X-trial, the investigators have planned to evaluate the effect of oxygen treatment on
IR-injury in STE-ACS as assessed by biomarkers reflecting various aspects of the pathological
processes involved.
The presented study is an experimental pilot study performed in healthy volunteers with a
Salmonella typhi vaccine-induced inflammation with the purpose of studying effects of oxygen
treatment on biological systems involved in the pathogenesis of IR- injury.