Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

Summary

Oxygen treatment is widely used in acutely ill patients, both pre-hospital and in hospital. The indication for oxygen is sometimes unquestionable, such as in many hypoxic patients, but in other situations its use is more of a practise and much less based on scientific evidence. In particular, oxygen treatment is routinely used in patients with a suspected heart attack and variably recommended in guidelines, despite very limited data supporting a beneficial effect. Indeed, a few studies even indicate that oxygen treatment might be harmful. Immediate re-opening of the acutely blocked artery to the heart muscle is the treatment of choice to limit permanent injury. However, the sudden re-initiation of blood flow achieved with primary percutaneous coronary intervention (PCI), the reopening and stenting of the blocked vessel, can give rise to further endothelial and myocardial 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, thrombocytes and white blood cells leading to extended inflammation and formation of clots are examples of those effects. The role of oxygen treatment on these pathological processes, on the extent of IR-injury and the final infarct size in patients with acute myocardial infarctions (AMI) has not previously been studied. In an ongoing national multicentre, randomized, registry based clinical trial, the DETO2X-AMI trial (NCT01787110), the effect of oxygen on morbidity and mortality in ACS patients is being investigated. The present DETO2X-biomarkers study is a substudy of the DETO2X-AMI trial, evaluating the effect of oxygen treatment on biological systems involved in the pathogenesis of reversible and irreversible myocardial damage and cell death in ACS.

Timeline

Start

2014-10

Primary completion

2015-12

Completion

2015-12

Publications

• Background Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2013 Aug 21;(8):CD007160. doi: 10.1002/14651858.CD007160.pub3.
• Background Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121-35. doi: 10.1056/NEJMra071667. No abstract available.
• Background Ekstrom M, Eriksson P, Tornvall P. Vaccination, a human model of inflammation, activates systemic inflammation but does not trigger proinflammatory gene expression in adipose tissue. J Intern Med. 2008 Dec;264(6):613-7. doi: 10.1111/j.1365-2796.2008.01998.x. No abstract available.
• Background Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507.
• Background Shuvy M, Atar D, Gabriel Steg P, Halvorsen S, Jolly S, Yusuf S, Lotan C. Oxygen therapy in acute coronary syndrome: are the benefits worth the risk? Eur Heart J. 2013 Jun;34(22):1630-5. doi: 10.1093/eurheartj/eht110. Epub 2013 Apr 3.
• Background Piper HM, Meuter K, Schafer C. Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg. 2003 Feb;75(2):S644-8. doi: 10.1016/s0003-4975(02)04686-6.
• Results Hofmann R, James SK, Svensson L, Witt N, Frick M, Lindahl B, Ostlund O, Ekelund U, Erlinge D, Herlitz J, Jernberg T. DETermination of the role of OXygen in suspected Acute Myocardial Infarction trial. Am Heart J. 2014 Mar;167(3):322-8. doi: 10.1016/j.ahj.2013.09.022. Epub 2013 Dec 19.
• Andell P, James S, Ostlund O, Yndigegn T, Sparv D, Pernow J, Jernberg T, Lindahl B, Herlitz J, Erlinge D, Hofmann R. Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease: a prespecified subgroup analysis from the DETO2X-AMI trial. Eur Heart J Acute Cardiovasc Care. 2020 Dec;9(8):984-992. doi: 10.1177/2048872619848978. Epub 2019 May 13.
• Hofmann R, Tornvall P, Witt N, Alfredsson J, Svensson L, Jonasson L, Nilsson L. Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction. J Intern Med. 2018 Apr;283(4):334-345. doi: 10.1111/joim.12716. Epub 2017 Dec 11.

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Indications