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: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Karolinska Institutet
• Collaborator: University Hospital, Linkoeping
• Treatments: Atorvastatin; Atorvastatin Calcium; Vaccines

Criteria

Inclusion Criteria:

• Age 18-40 years

• Male gender

Exclusion Criteria:

• Female gender

• Not willing to participate

• Not able to communicate or to understand study instructions

• Participation in another on-going trial

• Any chronic disease

• Any acute disease within 30 days of study inclusion

• Any regular or temporary medication within 15 days of study inclusion

• Current smokers